Sleep disturbance and fatigue in multiple sclerosis: A systematic review and meta-analysis

Abstract

Sleep disturbance is common in people with multiple sclerosis and may worsen fatigue; however, the assessment of sleep-fatigue relationships varies across studies. To better understand sleep-fatigue relationships in this population, we conducted a systematic review and random effects meta-analyses for the associations between fatigue and 10 sleep variables: Sleep-disordered breathing, daytime sleepiness, sleep quality, insomnia, restless legs, number of awakenings, sleep efficiency, sleep latency, sleep duration, and wake after sleep onset. Of the 1062 studies screened, 46 met inclusion criteria and provided sufficient data for calculating Hedges' g. Study quality was assessed using the Newcastle-Ottawa Scale. Sample characteristics did not differ between the 10 analyses. Results indicated that sleep quality and insomnia (assessed via self-report or diagnostic criteria) were strongly associated with fatigue (all gs ≥ 0.80 and all ps < .001). In contrast, the number of awakenings and sleep duration (assessed objectively) were not significantly associated with fatigue. Remaining sleep variables yielded moderate, significant effects. Most effects did not vary based on study quality or sample demographics. Results highlight that insomnia and perceptions of poor sleep have a stronger link than objective sleep duration to fatigue in multiple sclerosis and may represent a more effective target for intervention.

Keywords: (Medical subject headings): sleep initiation and maintenance; arousal; fatigue; multiple sclerosis; sleep apnea syndromes; sleep latency; sleep-wake disorders.

Figure 1.

Flow diagram of included studies. CINAHL: Cumulative Index to Nursing and Allied Health Literature; EMBASE: Excerpta Medica Database.

Figure 2.

Conceptual framework for categorization of 10 sleep variables predicting MS fatigue. Sleep variables identified based on a systematic search of the literature in PubMed, EMBASE, CINAHL/PsycINFO, and the Cochrane Library, and through data synthesis, with no category having fewer than 3 studies. CINAHL: Cumulative index to Nursing and Allied Health Literature; EMBASE: Excerpta Medica Database; MS: multiple sclerosis; PsycINFO: Psychological Information Database.

Figure 3.

Forest plot of associations between sleep and fatigue across 10 sleep categories. *p < .05; **p < .01; ***p < .001. EDS: excessive daytime sleepiness; INS: insomnia; NoA: number of awakenings; RLS: restless legs syndrome diagnosis; SDB: sleep-disordered breathing; SE: sleep efficiency; SQ: sleep quality; SOL: sleep onset latency; TST: total sleep time; WASO: wake after sleep onset.