Among patients with multiple sclerosis (MS), fatigue is the most commonly reported symptom, and one of the most debilitating. Despite its high prevalence and significant impact, fatigue is still poorly understood and often under-emphasized because of its complexity and subjective nature. In recent years, an abundance of literature from specialists in sleep medicine, neurology, psychiatry, psychology, physical medicine and rehabilitation, and radiology have shed light on the potential causes, impact, and treatment of MS-related fatigue. Though such a diversity of contributions clearly has advantages, few recent articles have attempted to synthesize this literature, and existing overviews have focused primarily on potential causes of fatigue rather than clinical evaluation or treatment. The aims of this review are to examine, in particular for sleep specialists, the most commonly proposed primary and secondary mechanisms of fatigue in MS, tools for assessment of fatigue in this setting, and available treatment approaches to a most common and challenging problem.

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 signifi cant 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. S C I E N T I F I C I N V E S T I G A T I O N SM ultiple sclerosis (MS) is an autoimmune disease of the central nervous system that causes myelin destruction and axonal damage in the brain and spinal cord. Multiple sclerosis is the leading cause of non-traumatic neurological disability among young adults, and is associated with a variety of debilitating symptoms, including fatigue.Fatigue affects up to 90% of multiple sclerosis patients at some point during their disease course.1-4 This highly debilitating symptom imposes signifi cant socioeconomic consequences 5 and is a leading cause of diminished quality of life among individuals with MS.3 Although MS-related fatigue is often multifactorial, identifi cation of treatable causes that may contribute to its severity is an essential element of management of this symptom.Obstructive sleep apnea (OSA) may exacerbate fatigue severity in MS. This treatable disorder of sleep and breathing is a known cause of fatigue and related symptoms in general population studies, 6 and constitutes a signifi cant risk factor for cardiovascular disease, metabolic syndrome, motor vehicle accidents, reduced productivity, cognitive dysfunction, and poor quality of life.7-14 Yet, despite its impact in the general population, the extent to which OSA contributes to fatigue in persons with MS is poorly understood, and the prevalence of OSA in MS remains unclear. Whereas some contend that the prevalence of OSA is higher in MS patients than in the general population, heterogeneity in subjects studied, sample sizes, and outcome measures have led to highly variable e...

Abstract:Patients with multiple sclerosis (MS) are at increased risk for comorbid sleep disturbances, which can profoundly contribute to poor functional status and fatigue. Insomnia, sleep-disordered breathing, and restless legs syndrome are among the most common sleep disorders experienced by patients with MS. Despite their impact, these underlying sleep disorders may escape routine clinical evaluations in persons with MS, thereby leading to missed opportunities to optimize functional status and quality of life in patients with MS. A practical, systematic approach to the evaluation and treatment of sleep disorders in MS, in the context of MS-specific variables that may influence risk for these conditions or response to therapy, is recommended to facilitate early diagnosis and successful treatment. This review summarizes the most common sleep disorders experienced by persons with MS, and offers a practical approach to diagnosis and management of these conditions.

Study Objectives To examine associations between PAP therapy, adherence and incident diagnoses of Alzheimer’s disease (AD), mild cognitive impairment (MCI), and dementia not-otherwise-specified (DNOS) in older adults. Methods This retrospective study utilized Medicare 5% fee-for-service claims data of 53,321 beneficiaries, aged 65+, with an OSA diagnosis prior to 2011. Study participants were evaluated using ICD-9 codes for neurocognitive syndromes [AD(n=1,057), DNOS(n=378), and MCI(n=443)] that were newly-identified between 2011-2013. PAP treatment was defined as presence of ≥1 durable medical equipment (HCPCS) code for PAP supplies. PAP adherence was defined as ≥2 HCPCS codes for PAP equipment, separated by≥1 month. Logistic regression models, adjusted for demographic and health characteristics, were used to estimate associations between PAP treatment or adherence and new AD, DNOS, and MCI diagnoses. Results In this sample of Medicare beneficiaries with OSA, 59% were men, 90% were non-Hispanic whites and 62% were younger than 75y. The majority (78%) of beneficiaries with OSA were prescribed PAP (treated), and 74% showed evidence of adherent PAP use. In adjusted models, PAP treatment was associated with lower odds of incident diagnoses of AD and DNOS (OR=0.78, 95% CI:0.69-0.89; and OR=0.69, 95% CI:0.55-0.85). Lower odds of MCI, approaching statistical significance, were also observed among PAP users (OR=0.82, 95% CI:0.66-1.02). PAP adherence was associated with lower odds of incident diagnoses of AD (OR=0.65, 95% CI:0.56-0.76). Conclusions PAP treatment and adherence are independently associated with lower odds of incident AD diagnoses in older adults. Results suggest that treatment of OSA may reduce risk of subsequent dementia.