Pain, sleep, stress linked to fatigue severity in relapsing-remitting MS

Among people with relapsing-remitting multiple sclerosis (RRMS) and mild to moderate disability, fatigue severity was associated with a range of physical and psychological factors that may be important to consider when managing the symptom, a study found.

Using patients’ responses to the Comprehensive Fatigue Assessment Battery for Multiple Sclerosis (CFAB-MS) — designed to assess fatigue and its contributing factors — the researchers found that greater disability, pain, sleep problems, stress, anxiety, and other factors were associated with higher levels of fatigue.

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Aug. 31, 2026 News by Marisa Horak, MS

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Fatigue assessment should look beyond symptom severity

The findings highlight the need to assess not only how severe the fatigue is, but also factors that may be associated with the symptom, the researchers noted.

“Recognizing and addressing these interrelated factors is essential to improving fatigue management and, ultimately, enhancing the quality of life for individuals living with MS [multiple sclerosis],” they wrote.

The study, “Fatigue and contributing factors in relapsing-remitting multiple sclerosis: a descriptive study based on the comprehensive fatigue assessment battery for multiple sclerosis (CFAB-MS),” was published in Neurological Sciences.

MS is marked by inflammation and damage to the myelin sheath, the protective covering around nerve fibers in the brain and spinal cord. It can cause a wide range of symptoms, including movement problems, fatigue, and cognitive and emotional difficulties.

Fatigue is one of the most common and disabling MS symptoms, affecting about 80% of patients. It can involve both physical and cognitive difficulties. It may result directly from MS or be worsened by other symptoms, complications, or medication side effects.

Several questionnaires can be used to assess fatigue in people with MS, but most focus primarily on how severe it is and may not capture factors associated with it. The CFAB-MS takes a broader approach, asking patients about different aspects of their health and daily life, including fatigue, pain, sleep, stress, mood, nutrition, mobility, environmental factors, and fatigue management strategies.

“Comprehensive assessment using the CFAB-MS may facilitate the identification of modifiable factors contributing to fatigue and support more personalized therapeutic decision-making,” the researchers wrote.

Study examines fatigue in mildly to moderately disabled RRMS patients

Here, a team of researchers in Iran used the CFAB-MS to analyze fatigue and factors associated with it in 123 RRMS patients who reported fatigue and had mild or moderate disability, defined as an Expanded Disability Status Scale (EDSS) score below four.

Participants’ mean age was 34.12 years, and 74.8% were women. They had been living with MS for a median of five years, and their median EDSS score was one.

The most common initial symptoms were blurred vision in women (34.8%) and sensory problems in men (41.9%). The most commonly used disease-modifying therapy was dimethyl fumarate (sold as Tecfidera with generics available; 35.8%), followed by fingolimod (sold as Gilenya and generics; 14.6%) and rituximab (sold as Rituxan, with biosimilars available; 14.6%).

According to the general health domain of the CFAB-MS questionnaire, the most commonly reported health problems were anxiety and worry, fatigue, and stress, while walking difficulties were the least reported issue. Anxiety and worry, as well as stress, were significantly more severe in women than in men.

In the fatigue domain, nearly half of participants (47.2%) reported experiencing fatigue for more than six months. Fatigue was reported occasionally by one-third of the patients, while 25.2% experienced it on most days and 23.6% daily. A higher proportion of participants reported fatigue lasting less than three hours per day. Fatigue most often started in the morning and worsened in the late evening.

Pain interfered with several aspects of daily life, and sleep disturbances were common. The most frequently reported disruptive factor during sleep was nighttime urination (52%). Other commonly reported sleep-related problems included restless legs syndrome (26.8%), morning headaches (26%), and sleep apnea (7.3%), a condition in which breathing repeatedly starts and stops during sleep.

Heat linked to worsening fatigue and lower energy

Among environmental factors, 70.7% of participants reported that heat worsened their fatigue, and 61% said their energy improved after leaving a hot environment.

Higher levels of disability based on EDSS scores were significantly associated with greater fatigue, pain, stress, anxiety, and walking difficulties, even though the study included only participants with mild to moderate disability.

More severe fatigue was also significantly associated with more severe pain, depression, anxiety, sleep problems, and walking difficulties. In addition, the physical, psychological, and social fatigue index was associated with all components of the general health domain, “reinforcing the interconnectedness of fatigue with a broad range of patient-reported outcomes,” the researchers wrote.

Overall, “these results highlight the multifactorial nature of fatigue in RRMS patients, with strong associations across physical, emotional, and behavioral domains,” the team concluded. “Symptomatic management of fatigue may include pharmacological agents, alongside non-pharmacological interventions such as structured exercise programs, diet therapy, cognitive behavioral therapy, energy conservation strategies, sleep optimization, and management of [co-existing] depression, anxiety, and pain.”

The researchers noted that the study’s cross-sectional design means it cannot establish cause and effect or determine which factors were independently associated with fatigue. They also noted poor reliability in some measures of sleep, mood, and pain.