Current challenges in defining, measuring and treating MS-related fatigue

Kessler Foundation researcher John DeLuca, PhD, published an important clinical article in Journal of Neurology, shedding light on the fleeting nature of fatigue in multiple sclerosis (MS) and its implications for treatment. The study provides a comprehensive review of current challenges in defining, measuring and treating MS-related fatigue, offering new insights and directions for future research.

The open access article, “Fatigue in multiple sclerosis: can we measure it and can we treat it?” (Doi: 10.1007/s00415-024-12524-9), published 5 July 2024. It highlights the multidimensional nature of fatigue, highlighting the ongoing struggle to precisely define it and measure it effectively. Dr. DeLuca identified over 250 scales used to assess fatigue, but noted significant content validity issues, raising questions about their effectiveness.

“Our ability to identify, measure and treat fatigue in MS has improved only marginally despite over a century of research,“ said Dr. DeLuca, senior vice president for research and training at the Foundation. “This study highlights the need for innovative approaches to better understand and treat this complex symptom. It also highlights the need to distinguish fatigue from other related symptoms and develop more accurate measurement tools. Addressing these challenges is crucial to improving the quality of life for people with MS.“

Fatigue affects up to 90 percent of people with MS, significantly affecting their daily life. Despite its prevalence, the definition of fatigue remains difficult due to its subjective and multifaceted nature. The article examines historical and contemporary definitions of fatigue, criticizes existing measurement tools for lack of clarity and consistency, and explores the subjective nature of fatigue and its association with other symptoms such as depression, pain, and cognitive complaints.

In addition, Dr. DeLuca examines the brain’s role in fatigue, suggesting that disturbances in the cortico-striatal-thalamic-cortical loop contribute to central fatigue. “Advanced MRI imaging techniques have shown that central fatigue is associated with disturbances in this brain network. Recent research shows that motivation can reduce fatigue by stimulating the fronto-striatal network, suggesting new potential therapeutic approaches,” he pointed out.

How can we deal with fatigue?

The study examines both pharmacological and non-pharmacological treatments for fatigue in MS. Pharmacological treatments, such as amantadine, modafinil, and methylphenidate, have shown limited efficacy. Conversely, the article also explores non-pharmacological treatments for fatigue, such as cognitive-behavioral therapy and exercise, which have shown moderate to large effects in reducing fatigue symptoms. In addition, the possibility of new approaches involving the brain’s reward system is reported, suggesting that motivational stimuli could play a critical role in the management of fatigue in MS patients.

This research was supported in part by National Multiple Sclerosis Society (NMSS) grant MB-2107–38097 and funding from the Kessler Foundation.