Looking for signs of inflammation in the brain of Chronic Fatigue Syndrome Patients

Rationale: Chronic Fatigue Syndrome (CFS) is a disease of unknown origin characterized by the presence of severe disabling fatigue for a period of at least six months. Patients often are diagnosed after having symptoms for several years, as there is no accurate diagnostic tool to diagnose CFS. This leads to a delay in starting treatment.



Q Fever fatigue syndrome (QFS) is a well documented state of prolonged fatigue following acute Q fever, an infection caused by Coxiella burnetii. Up to 20% of patients diagnosed with acute Q fever will eventually develop QFS, leading to a substantial burden for those who are affected. The clinical presentation of QFS sometimes shows overlapping symptoms with the symptoms of CFS patients. As is the case with CFS, research is still focused on finding better tools for diagnosing and treating this disease.



To improve diagnosis and treatment it is important to understand the mechanisms underlying these diseases. It has been proposed that (neuro)inflammation is an important factor in the development of CFS. We therefore aim to assess whether CFS and QFS are accompanied by the presence of neuroinflammation, using Positron Emission Tomography (PET).



Objective: The primary objective of this study is to evaluate whether there is an increased binding potential of the TSPO ligand [11C]PK11195, which is a marker for microglia activation in neuroinflammation, using PET in patients with CFS compared to patients with QFS and healthy age- and sexe-matched controls. Secondary objective(s) are to correlate the binding potential of [11C]PK11195 to (1) MRI measurements in the same subjects, (2) to fatigue severity using the CIS fatigue questionnaire and (3) to peripheral cytokine concentrations.



Study design: The design of this study is observational and case control, comparing the presence of neuroinflammation between CFS patients, QFS patients and healthy age- and sexe-matched controls.



Study population: The study population will consist of 10 CFS patients, 10 QFS patients and 10 healthy age- and sexe-matched controls subjects, which are neighbourhood controls. All subjects are females with an age between 18 and 60 years old.



Intervention: The subjects will undergo a PET scan with the TSPO ligand [11C]PK11195, which is a marker for microglia activation in neuroinflammation.



Main study parameters/endpoints: The main study parameter is the [11C]PK11195 binding potential in the brain.

Investigate if Chronic Fatigue Syndrome patients show signs of neuroinflammation, compared to Q-fever Fatigue Syndrome (QFS) patients and healthy neighbourhood controls.

There is one timepoint on which all measurements will be conducted.

[11C]PK11195 (a ligand for the TSPO protein, upregulated in activated microglia cells) is injected in both patients, and healthy age- and sexe-matched controls. Binding of this tracer will be visualised on PET scan, indicating degree of neuroinflammation (activated microglia cells).