Kessler scientists using $700K grant to study primary fatigue in MS

A team of Kessler Foundation researchers has been granted more than $700,000 by the National Multiple Sclerosis Society for work that seeks to better understand the brain networks associated with primary fatigue in people with multiple sclerosis (MS).

The grant, totaling $722,602, was awarded to Glenn Wylie, PhD, director of Kessler’s Rocco Ortenzio Neuroimaging Center, in New Jersey.

The three-year research project, titled “Establishing a clearer measure of cognitive fatigue in Multiple Sclerosis: State vs. Trait,” will be focused on identifying new methods to measure this symptom as it’s directly attributed to MS-related nerve cell damage. A key goal is to differentiate so-called primary fatigue from it occurring as secondary to other disease symptoms.

The findings may ultimately help to advance treatments for MS fatigue, and to improve life quality for those with the neurodegenerative disease.

“By redirecting focus towards understanding and alleviating primary fatigue, our research aims to substantially improve the quality of life for individuals living with MS, whose daily activities are often severely constrained by debilitating fatigue,” Wylie, the project’s lead investigator, said in a foundation press release.

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Research to focus on primary vs. secondary fatigue in MS

Fatigue, defined as mental or physical exhaustion that prevents a person from performing their daily activities, is estimated to impact about 80% of people with multiple sclerosis. This has a significant impact on quality of life, but more research is needed to better understand how to ease this symptom in MS.

That’s because this common problem can have multiple causes. It can be primary, where the symptom arises directly as a result of inflammatory damage to nerve cells — which, in turn, makes it harder to get needed nerve cell information to other parts of the body. Or, it can be secondary, resulting indirectly from other MS symptoms, such as depression, stress, or sleep disorders, or from medication side effects.

However, it is difficult to objectively measure either way, and currently used assessment tools cannot distinguish between primary and secondary fatigue.

“Previous investigations into fatigue have predominantly focused on secondary factors such as sleep disturbances or depression, failing to adequately capture the essence of primary fatigue directly resulting from MS,” Wylie said.

The lack of information led Wylie to launch his trait versus state project. Recent findings have proposed that “state” assessments reflect acute experiences, providing an accurate evaluation of primary fatigue. Meanwhile, “trait” assessments measure the symptom over extended periods, in which it represents a secondary issue.

Previous investigations into fatigue have predominantly focused on secondary factors such as sleep disturbances or depression, failing to adequately capture the essence of primary fatigue directly resulting from MS.

Building on that, Wylie and his team have developed behavioral and imaging methods to evaluate fatigue in MS and are conducting tests to validate those approaches in clinical research.

First, the researchers will use challenging tests to induce cognitive fatigue in MS patients, with their approaches then used to objectively assess the impact of this symptom in the brain. The team also will assess which brain regions are activated during tasks, and how different parts of the brain are connected when people experience fatigue.

“Our study aims to validate ‘state’ measures of fatigue, offering a more accurate assessment of primary fatigue through correlation with objective performance and brain activation patterns,” Wylie said.

“We will do this by employing neuropsychological testing, functional neuroimaging, and connectivity mapping,” Wylie said.

The validation of these measures, according to the Kessler Foundation, will contribute to the development of solutions for treating MS-related fatigue, for which there are few available treatment options.

The National MS Society, which dates back to 1946, has invested more than $1.1 billion into research to date to advance the understanding of and treatments for multiple sclerosis.