Orthostatic Intolerance in ME/CFS: Characterization of Subtypes and Cerebral Blood Flow regulation
Orthostatic intolerance (OI) is a condition in which sitting or standing upright causes dizziness, palpitations, or fainting. OI can take several forms, one of which is Postural Orthostatic Tachycardia Syndrome (POTS). Between 40% and 90% of ME/CFS patients experience OI, leading to significant discomfort.Despite its prevalence, little is known about the underlying causes of OI, and diagnosis remains challenging. Typically, OI is diagnosed based on changes in blood pressure or heart rate during posture tests. However, in about half of the patients who report OI symptoms, these tests show no abnormalities.
Recent research has revealed that individuals with OI often experience reduced cerebral blood flow (CBF) during posture changes. This finding provides an important explanation for OI symptoms and offers new opportunities for improving diagnostic accuracy.
Objective
The aim of this project is to improve diagnostic precision and understanding of OI in ME/CFS. This will be achieved through two complementary studies:
- Study 1 focuses on identifying distinct subtypes of OI in ME/CFS. A comprehensive analysis will be performed on physical (physiological), perceptible (symptomatic), and daily functioning (functional) data from the Dutch ME/CFS Cohort and Biobank (NMCB). The goal is to classify different OI forms into categories to enhance understanding of diagnostics and disease progression.
- Study 2 applies advanced MRI techniques to investigate how reduced cerebral blood flow contributes to OI symptoms.
Approach / Method
Study 1 uses data from the NMCB cohort. It analyses responses to the NASA Lean Test, a validated method for assessing OI. This includes measurements of symptoms, autonomic nervous system function, and cognitive performance. Data from 750 ME/CFS patients will be compared with data from 450 healthy controls. In parallel, researchers will analyse comparable data from patients with post-COVID, post-Q fever, and post-Lyme.
In Study 2, Lower Body Negative Pressure (LBNP) is used to simulate orthostatic stress while participants lie in an MRI scanner, allowing real-time imaging of the brain. This approach enables researchers to assess how reduced cerebral blood flow contributes to OI symptoms. The study will compare 50 ME/CFS patients with severe OI, 25 ME/CFS patients without OI, and 25 healthy controls.
Collaboration Partners
This multidisciplinary clinical research team combines expertise from multiple fields, including neurology, cardiology, and (neuro)radiology (Leiden UMC, Amsterdam UMC, Stichting Cardiozorg), as well as data science and bioinformatics (Amsterdam UMC, University of Amsterdam). This broad collaboration accelerates the translation of research findings into clinical practice.
Representatives from three patient organisations — ME/CVS Nederland and ME/cvs Vereniging— are actively involved in the study’s design, implementation, interpretation, and dissemination. Their participation ensures that the research aligns with the needs and priorities of patients.
There is also close collaboration with international experts in OI and ME/CFS from the United States, Germany, Sweden, and the United Kingdom.
Expected Results
The project aims to achieve improved diagnostic methods for OI in ME/CFS. MRI imaging may provide a new diagnostic tool to identify abnormalities in cerebral blood flow. Better objective measurement of OI in ME/CFS will form a foundation for future treatment research and contribute to a deeper understanding of the disease.