Fatigue is a common symptom of MS but its mechanism remains poorly understood

Multiple sclerosis, or MS, is the most common autoimmune disease of the central nervous system. People with MS often experience fatigue that significantly interferes with function. The exact mechanisms of fatigue remain unknown. More information is needed on the underlying causes in order to develop new and more effective treatment methods.

Published: 25.8.2022
Writer: Eero Rissanen
Picture: Shutterstock


Most commonly diagnosed in young adults, multiple sclerosis, or MS, is an autoimmune disease in which the body’s own immune system interprets structures of the central nervous system as foreign intruders and starts to attack them. An autoimmune reaction causes inflammation and damage to nerve cells, or neurodegeneration. Medications currently available can effectively reduce and slow down both processes. Despite medication, fatigue is an unpleasant companion for many people with MS.


As many as 60–80 per cent of people with MS suffer from fatigue

In MS, the overactivation of microglia, the brain’s immune cells, is essentially related to neuroinflammation. This process may be suppressed by noradrenaline (or norepinephrine), a neurotransmitter of the sympathetic nervous system, which regulates the level of alertness in the brain. Damage to the noradrenaline-producing areas of the brain is thought to weaken the activity of the sympathetic nervous system and thereby contribute to MS-related fatigue.

At some stage of the disease, as many as 60–80 per cent of patients feel that severe fatigue is the most debilitating symptom. Treatments currently available for fatigue have had a limited effect, and the mechanisms of MS-related fatigue are poorly understood. It is likely that excessive inflammation of the nervous system and changes in the amount and function of neurotransmitters that regulate alertness play a role in this.


A PET scan shows how the brain functions

Convincing research evidence on the connections between microglia and the activity of the noradrenaline system in humans is still lacking. While studying the living brain is not possible with conventional imaging methods, positron emission tomography (PET) enables the imaging of cellular and neurotransmitter-level phenomena in humans in vivo. A PET scan uses a very small amount of radioactive tracers that transiently bind to the desired targets in the brain.

During my research fellowship at the Harvard Medical School in Boston, I had the opportunity, with support from the Sakari Alhopuro Foundation, to continue my work in a multidisciplinary research project as a member of the research team of Assistant Professor Tarun Singhal. The purpose of the project is to conduct an in vivo study to establish a connection between the activation of microglia, changes in the cerebral noradrenaline system, and MS-related fatigue and structural damage in the brain. 

The study involves combining the use of new [18F]PBR06 and [11C]MRB markers that bind to activated microglia and the noradrenaline transporter protein with a PET scan. In addition, a 7-Tesla MRI scanner is used to obtain more detailed images of brain structures.


Hoping to discover more effective treatment methods

The study is expected to provide important information on the mechanisms of MS-related fatigue and their linkage to neuroinflammation and structural changes in the nervous system. Furthermore, the research results are hoped to advance the development of medications that affect the course of the disease and symptomatic treatment. With new therapies, we will be able to provide a wider range of more effective support to MS patients, helping them to remain active.



Petri Rissanen.


Eero Rissanen, MD, PhD, Adjunct Professor, and Neurology Consultant, is the Chief Physician and Neurology Consultant at the Neurology Outpatient Clinic in the Tyks Vakka-Suomi Hospital since 2013. Rissanen earned his Ph.D. in medicine from the University of Turku in 2015. Since December 2019 he was a research fellow in  the PET imaging research programme led by Dr. Tarun Singhal, MBBS, MD, Assistant Professor and Associate Neurologist at the Ann Romney Center for Neurologic Disease, Brigham and Women's Hospital and Harvard Medical School. Rissanen is currently the director of Neurocenter Finland at the University of Eastern Finland.





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