Sleep Apnea Common in MS-Related Fatigue

Nancy A. Melville

March 08, 2019

DALLAS — Among people with multiple sclerosis (MS) who experience the highly common symptom of fatigue, the majority have obstructive sleep apnea (OSA), new research suggests.

The finding suggests an important window of opportunity for effective treatment when so many other causes of fatigue in MS may be either unclear or untreatable, researchers say.

The results underscore that "undiagnosed OSA is common in people with MS who report fatigue," said the authors of research presented here at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2019.

"OSA incidence in people with MS increases with Expanded Disability Status Scale (EDSS, a key measure of MS severity), but is still common in those with low EDSS scores," they note.

Likewise, "while OSA is more common in people with high body mass index (BMI), low BMI does not preclude a diagnosis of OSA," said the authors, led by neurologist Mark Gudesblatt, MD, of South Shore Neurologic Associates, in Patchogue, New York.

The study, said to be the largest of its kind to evaluate obstructive sleep apnea in MS, involved 292 patients with MS who reported symptoms of fatigue and participated in overnight polysomnography (PSG) sleep studies at the South Shore Neurologic Associates center.

Of the patients, 81.4% were women, with an average age of 47.  

Results from the overnight PSG showed that 61% (177) of the patients had obstructive sleep apnea, defined as having an Apnea-Hypopnea Index (AHI) score of 5 or higher.

Consistent with the general population, OSA increased substantially with age: While OSA was observed in just 26% (n = 19) of those under the age of 30, the rate increased to 52% in those ages 30 to 40 (n = 62); to 58% among ages 40 to 50 (n = 106); 73% in those 50 to 60 (n = 75); and 82% in those over age 60 (n = 28).

But while 71% of those who were overweight or obese (BMI 28 or higher [n=131]) had OSA, as many as 57% (n = 93) of those with BMI lower than 28 also had OSA.

In terms of MS symptom severity, of those with EDSS scores of 0 to 2.5 (n = 96), 57% had OSA; for EDSS 3.0 to 5.5 (n = 25), the rate climbed to 63%; and for EDSS scores between 6.0 and 8.0 (n = 25), as many as 89% had OSA.

OSA rates increased with disease duration, but only for longer term. For those with MS duration of less than 5 years (n = 130), and in the 5- to 10-year bracket (n = 76), the rate of OSA stayed the same — 57%; for disease duration between 10 and 15 years (n = 51), the rate increased to 67%, and for disease duration greater than 15 years (n = 18), OSA was observed in 72%.

The findings offer important insights considering that fatigue is among the most common and disabling symptoms in MS, but clinicians are largely reliant on patient self-reports in their awareness of the presence of fatigue, and its degree of severity, the authors said.

"Patient-reported information relating fatigue, sleep disturbance, and the presence of OSA may be unreliable," the researchers note.

In a separate analysis of the same cohort, the investigators found that among the 292 reporting fatigue, 55% had an Epworth Sleepiness Scale (ESS) score of less than 10 and 45% had an ESS score greater than 10 (n = 95), indicating the presence of sleep disorders.

Among the 61% of MS patients with OSA, most of them (82% [n = 148]) had high fatigue, defined as a Fatigue Severity Scale (FSS) score of 36 or higher.

Role of Neural Network Disruptions in OSA Speculated

While little is understood on the possible mechanisms linking OSA to MS, senior author Gudesblatt speculated that compromised neural networks may be a factor.

"Upper airway entrance architecture plays a key role in airway obstruction," he told Medscape Medical News.

"But likely, the disruption of neural networks disconnects the sleep initiation maintenance of the regulation/relaxation, synchrony, muscle or tissue relaxation, contributing to some of the OSA." 

Furthermore, the OSA may, in addition to causing some aspects of fatigue, have other adverse effects on MS, Gudesblatt suggested.

"The contribution of the inflammatory aspects of the OSA might worsen the MS or change efficacy of disease modifying therapies (DMTs)."

OSA is known to respond well to treatments such as Continuous Positive Airway Pressure (CPAP) therapy, and while sleep apnea may seem a relatively small piece of the puzzle amid the abundant challenges in MS treatment, any improvements in sleep could indeed have important benefits.

"Sleep deprivation impacts fatigue, mood, and cognition, and they are all intertwined, like instruments in an orchestra," Gudesblatt said. 

"It is these multidimensional aspects that reflect the paths to identifying disability progression in MS — not unidimensional aspects or information," he said.

Furthermore, metrics that are standard in neurology measuring things like sleep too often fall short in assessing the nuances that may be more important than realized, Gudesblatt asserted.

He noted the shortcomings of the basic question, "How do you sleep?"

"How does someone know how they sleep?" he said. "They are asleep — you know where you start and where you finish — but not the middle. A better question is, 'Do you awaken refreshed or tired?' "

In something as complex as MS, "treatment may be ineffective unless each fatigue-generating factor is meticulously picked apart and proactively treated," Gudesblatt added.

Diligence in Dissecting Causes of Fatigue

In fact, guidelines for addressing fatigue in MS call for such diligence, Ruth Ann Marrie, MD, PhD, a professor of medicine and community health sciences at the University of Manitoba in Winnipeg, Canada, told Medscape Medical News.

"Algorithms for the management of fatigue in MS emphasize the importance of identifying and treating secondary causes of fatigue, such as sleep disorders, anemia, and hypothyroidism, before assuming that the fatigue is primarily due to MS," she said.

And while those issues may be high on neurologists' radars, challenges remain in research, Marrie said.

"Clinically, I think neurologists are aware of sleep disorders as a comorbidity that occurs with increased frequency in people with MS, and that they are associated with fatigue and other outcomes," she said.

"From a research perspective, they may have received somewhat less attention (although they are studied) because practically they are harder to study, as they involve costly sleep studies."

The study authors have disclosed no relevant financial relationships. Marrie has received research funding from CIHR, MS Society of Canada, the CMSC, the Waugh Family Chair in Multiple Sclerosis, Crohn's & Colitis Canada, and Research Manitoba.

Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2019. Abstracts 53, 54. Presented March 1, 2019.

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