Conference Coverage

Abnormal Sleep Staging Predicts Fatigue in Patients With MS

REM sleep onset latency, sleep-related movement, and subjective insomnia are associated with MS-related fatigue.


BALTIMORE—Objective and subjective sleep measures are associated with fatigue in people with multiple sclerosis (MS), according to a meta-analysis presented at the 32nd Annual Meeting of the Associated Professional Sleep Societies.

Jagriti “Jackie” Bhattarai, PhD

Evidence suggests that individuals with MS have disruptions in sleep that are associated with and may contribute to fatigue, said Jagriti “Jackie” Bhattarai, PhD, a postdoctoral fellow in the MS Rehabilitation Research Laboratory at the Johns Hopkins School of Medicine’s Department of Physical Medicine and Rehabilitation in Baltimore. Among the sleep parameters investigated, sleep staging, sleep-related movement, and subjective insomnia had moderate associations with fatigue. Other sleep parameters examined in the study were not statistically significantly associated with fatigue, she said.

A Major Factor in Disability

Fatigue is a leading contributor to disability in patients with MS. Although fatigue is a complex symptom with multiple neurologic and behavioral causes, emerging evidence suggests that “sleep disturbance may have a significant role in the development or maintenance of fatigue in MS,” Dr. Bhattarai said. The relationship between sleep parameters and fatigue in people with MS is not well understood, however, she said.

To examine the relationship between commonly used sleep parameters and fatigue in MS, Dr. Bhattarai and colleagues identified studies that included at least one validated measure of fatigue and one validated measure of sleep disturbance. They included studies that reported the effect sizes of the associations between sleep and fatigue or provided enough data for the investigators to compute the effect sizes.

Their meta-analysis included 37 studies with 6,129 participants. Participants had an average age of 42 and MS duration of 9.5 years. About 80% of the sample had relapsing-remitting MS.

Sleep measures included polysomnography, actigraphy, and the multiple sleep latency test, as well as subjective measures such as the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, and the Medical Outcomes Study Sleep Scale.

Fatigue was measured using the Fatigue Severity Scale, the modified Fatigue Impact Scale, or the Neurological Fatigue Index for MS.

Effect sizes varied across studies, as did the parameters examined within each study. The mean effect size was the largest for the association between REM sleep onset latency (ie, the time between sleep onset and initiation of REM sleep) and fatigue (r = 0.42), though this effect size was based on only two studies, and the association requires further investigation. “Shorter REM sleep onset latency has been associated with depression and narcolepsy,” both of which are more common in people with MS than in the general population, Dr. Bhattarai said. Subjective insomnia (r = 0.36) and objective sleep-related movement (r = 0.34) also yielded moderate effect sizes. “The shorter the REM sleep onset latency and the more subjective complaints that individuals have about their sleep, the greater the level of fatigue people with MS reported,” she said. “The more sleep-related movement that people have, the greater their level of MS-related fatigue.”

Potential to Inform Treatment Approach

The association between fatigue and objective sleep-disordered breathing was not statistically significant. Subjective sleep-disordered breathing, objective nocturnal arousals, sleep efficiency, sleep onset latency, and sleep duration had weak effect sizes. These problems are common and require treatment, however, Dr. Bhattarai said.

“When treating patients with MS who are experiencing MS-related fatigue, interventions geared toward improving patients’ perceived sleep quality and addressing MS symptoms that might disrupt sleep (eg, nocturia and periodic leg movements) may offer an avenue for improving fatigue,” said Dr. Bhattarai. “However, these effects remain to be shown in a randomized controlled trial.”

—Jake Remaly

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