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ME/CFS and related chronic complex diseases

Brain Nuclear Inflammation

This study is led by Ronald Tompkins, PhD, and Wenzhong Xiao, PhD, in collaboration with Michael VanElzakker, PhD, and David Systrom, MD.

This project aims to better understand the role of neuroinflammation in ME/CFS.

Dr Michael VanElzakker developed a hypothesis that microglial cells become activated in critical brain nuclei creating a form of neuroinflammation, which affects normal function of multiple brain nuclei including those in the brainstem, during the development of the ME/CFS disease. Microglia are immune cells of the brain and microglial activation can be attributed to the vagus nerve, a nerve that meanders through the torso connecting majority of the organs to the brain.

There is ample evidence that low grade inflammation is present in ME/CFS patients at all times when the disease is active and this inflammation might be very significant during periods of flares. This peripheral inflammation can either be spread directly to the central nervous system (CNS) via porous portions of the blood brain barrier or via the vagus nerve.

There are two ongoing MRI and PET imaging studies that result of a collaboration between Drs. Michael VanElzakker and David Systrom.

  1. The current and ongoing MRI/PET study is beginning to demonstrate important metabolic findings associated with ME/CFS symptoms. This project aims to use high-resolution functional Magnetic Resonance Imaging (fMRI) including Magnetic Resonance Spectroscopy (MRS) to study 30 patients with ME/CFS relative to healthy controls. Participants will first undergo Vagal Nerve Stimulation (tVNS) and breathing challenges outside of the scanner to ensure they are appropriate for the study. Inducted participants’ brains will then be scanned both before and 1-3 days after an exercise challenge. These scans will allow metabolites in the brain to be quantified and the degree of blood perfusion through the brain to be measured.
  2. This study will focus on an improved design of the 2014 study by Nakatomi that observed neuroinflammation in the brainstem using Positron Emission Tomography (PET).

This clinical research by the Collaboration takes advantage of two world class MRI and PET centers at MGH – The Athinoula A. Martinos Center for Biomedical Imaging and The Gordon Center for Medical Imaging. These facilities offer outstanding opportunities to observe microglial activation and how they relate to metabolism changes consistent with the hypothesis.

Read more at the Harvard site

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