J Clin Sleep Med. 2014 Feb 15;10(2):155-62. doi: 10.5664/jcsm.3442.
Obstructive sleep apnea and fatigue in patients with multiple sclerosis.
- 1University of Michigan Department of Neurology and Multiple Sclerosis Center, Ann Arbor, MI ; University of Michigan Department of Neurology and Sleep Disorders Center, Ann Arbor, MI.
- 2University of Michigan Department of Neurology and Multiple Sclerosis Center, Ann Arbor, MI.
- 3University of Michigan Department of Neurology and Sleep Disorders Center, Ann Arbor, MI.
STUDY OBJECTIVES: The prevalence of obstructive sleep apnea (OSA) in persons with multiple sclerosis (MS) remains unknown, and little information exists regarding the relative contributions of OSA to symptoms of MS-related fatigue in the presence of other clinical and sleep-related confounders. The objectives of this study were to investigate the prevalence of diagnosed OSA and OSA risk among MS patients, and to assess relationships between fatigue severity, OSA, OSA risk, and sleep quality among persons with MS.
METHODS: N = 195 MS patients completed a questionnaire comprised of items regarding OSA diagnosis, sleep quality and quantity, daytime symptoms, and 4 validated scales: the Epworth Sleepiness Scale, Fatigue Severity Scale, Insomnia Severity Index, and STOP-Bang questionnaire. Medical records were also accessed to examine clinical characteristics that may predict fatigue or OSA risk.
RESULTS: N = 41 patients (21%) carried a formal diagnosis of OSA. N = 110 (56%) of all patients, and 38 (93%) of those with diagnosed OSA had STOP-Bang scores ≥ 3, indicating an elevated OSA risk. In regression models, the most significant predictors of higher FSS scores were higher STOP-Bang scores (p = 0.01), higher number of nocturnal symptoms (p < 0.0001), and higher disability level (p < 0.0001).
CONCLUSIONS: Sleep disturbances, and OSA in particular, may be highly prevalent yet underrecognized contributors to fatigue in persons with MS.
KEYWORDS: STOP-Bang; fatigue; multiple sclerosis; obstructive sleep apnea; sleep disturbance
Multiple sclerosis (MS) is a chronic, autoimmune disease that causes brain and spinal cord damage. In addition to neurological disability, MS patients suffer from a variety of chronic symptoms, including fatigue.1 While many MS patients consider fatigue to be one of their most debilitating symptoms with respect to quality of life,2 it is also one of the most challenging and complex symptoms to treat, in part because of its multifactorial nature. Interestingly, MS patients are also at increased risk for several sleep disorders, including obstructive sleep apnea (OSA) – a chronic disorder characterized by upper airway collapse during sleep.3 In addition to sleepiness and cardiovascular consequences, previous work suggests that OSA is associated with fatigue in MS,4, 5 but the extent to which OSA contributes to fatigue in the context of other potential sleep disturbances, medications, and MS-related variables remains poorly understood. Furthermore, although most clinicians accept that MS patients are at increased risk for OSA and other sleep disorders, OSA prevalence estimates in MS have varied widely across studies. To improve functional outcomes in patients with MS, not only is necessary to understand the scope of OSA under-recognition, but also the impact of OSA on chronic symptoms such as fatigue. In this study, we sought to explore the extent to which sleep disturbances, and OSA in particular, contribute to fatigue in MS patients.
We conducted a comprehensive survey study of nearly 200 patients with a confirmed diagnosis of MS followed in a large tertiary MS center to determine the proportion of patients who carried a diagnosis of OSA, or were at risk for OSA, based a commonly used 8-item screening tool known as the STOP-Bang Questionnaire (scores of 3 or higher indicate elevated risk for OSA).6, 7 We then assessed relationships between OSA, OSA risk, and fatigue level – which was measured using a validated instrument known as the Fatigue Severity Scale (FSS).8 Insomnia severity, symptoms of restless legs syndrome (RLS), sleep quality, sleep quantity, and sleepiness were also assessed. Our analyses also included an estimation of the Population Attributable Risk % (PAR%) – an estimate the proportion of fatigue (defined here as FSS score ≥ 4) among MS patients that would be eliminated by diagnosis and successful treatment of the underlying OSA or elevated OSA risk. Additional data regarding nocturnal symptoms that interfere with sleep (including pain, tingling, spasticity, feelings of restlessness, urinary urgency, anxiety, an inability to shut off the mind, and muscle twitching) were also collected through multiple choice questions.
Our findings showed that one-fifth of multiple sclerosis (MS) patients sampled carried a diagnosis of OSA, and a substantially higher proportion of patients (more than half) were found to be at elevated risk for OSA based on the STOP-Bang Questionnaire.6 Furthermore, OSA risk (as defined by the STOP-Bang) emerged as a significant predictor of fatigue in multivariate analyses, after adjustment for other several important sleep- and MS-specific variables that are associated with fatigue. The PAR% for diagnosed OSA as a risk factor for fatigue in MS patients was 11%. The PAR% for elevated OSA risk as a risk factor for fatigue was 40%. Thirty percent of responders met clinical diagnostic criteria for RLS.9 For 109 patients who endorsed difficulty sleeping on a single item question, 46% of these subjects met criteria for moderate clinical insomnia as defined by the Insomnia Severity Index.10 Eighty-five percent of patients endorsed at least one nocturnal symptom to interfere with their ability to get a good night’s sleep, with 54% of patients endorsing ≥ 3 of these symptoms.
We were particularly surprised by the difference between the proportion of patients who carried an established diagnosis of OSA (21%) and those at risk for OSA based on STOP-Bang scores (56%), highlighting an important discrepancy between OSA risk and recognition in this population. We were also struck by our PAR% estimations, which suggested that that a substantial portion of MS-related fatigue—between 11% and 40%—could be eliminated by diagnosis and successful treatment of OSA in patients with MS.
Our data provide new evidence that OSA is underdiagnosed in MS patients, and that OSA in particular may be a highly prevalent and yet under-recognized contributor to fatigue in persons with MS. The identification of treatable conditions that may contribute to MS fatigue severity is an essential component of managing this common and debilitating symptom. Our study highlights the impact that OSA and other sleep disturbances may have on fatigue in MS, and suggests that clinicians should have a low threshold to evaluate MS patients for underlying sleep disturbances.
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- Braley TJ, Segal BM, and Chervin RD. Obstructive sleep apnea and fatigue in patients with multiple sclerosis. J Clin Sleep Med 2014: 10(2); 155-162.
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- Krupp LB, LaRocca NG, Muir-Nash J, and Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 1989: 46(10); 1121-1123.
- Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, and Montplaisi J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003: 4(2); 101-119.
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