Elsevier

Sleep Medicine Reviews

Volume 14, Issue 2, April 2010, Pages 121-129
Sleep Medicine Reviews

Clinical Review
Sleep disorders in patients with multiple sclerosis

https://doi.org/10.1016/j.smrv.2009.07.005Get rights and content

Summary

Patients with multiple sclerosis (MS) often have unrecognized sleep disorders at higher frequency than the general population. Sleep disorders such as sleep disordered breathing, insomnia, REM sleep behavior disorder, narcolepsy and restless legs syndrome have all been reported in the MS population. Notably, the most common symptom of MS is “fatigue,” which itself has been correlated with sleep disturbances. Sleep disorders may impact the quality of life of the MS patient population. This paper reviews the association of sleep disorders with MS, and discusses the association of sleep disruption with MS fatigue.

Introduction

Multiple sclerosis (MS) is a chronic central nervous system autoimmune demyelinating disease that most commonly affects people between the ages of 20 and 50 years, with a worldwide prevalence of approximately 2.5 million people.1 The disease is characterized by relapsing and remitting neurological symptoms, such as weakness, numbness, vertigo, cognitive changes and blindness, leading long term to physical disability.

Though often unrecognized, sleep disorders are seen in the MS population at higher frequency than the general population, with estimates ranging from 25% to 54% based on small series of patients.2, 3, 4, 5, *6, *7 Sleep disorders such as insomnia, sleep disordered breathing, circadian rhythm disorder, restless legs syndrome (RLS), narcolepsy and rapid eye movement (REM) sleep behavior disorder have all been reported in the MS population. These findings merit further attention given the potential impact of sleep disorders on the health and quality of life in individuals living with MS.4, *6 Sleep disturbances have been associated with increased risk of mortality, cardiac disease, obesity and diabetes,8, 9, 10, 11 and can contribute to depression, pain and fatigue – symptoms that are commonly seen in MS patients, and that are often disabling.2, 3, 4, 5, *6, *7

The goal of the review is to review our current knowledge of sleep disorders in the MS population. In addition to examining specific sleep disorders, we will discuss the additional features specific to MS that may contribute to sleep disruption. We aim to raise awareness of sleep disorders in the MS population, with the ultimate goal of providing guidance concerning diagnosis and treatment. We discuss the intricate relationship between sleep and the immune system with respect to MS, and close with recommendations for further research.

Section snippets

Narcolepsy

Narcolepsy is classified as a chronic sleep disorder associated with sleep attacks and other features attributed to abnormalities of REM sleep, such as hypnagogic/hypnopompic hallucinations, cataplexy, sleep paralysis, and disrupted nocturnal sleep.12 The usual polysomnographic features include a mean sleep latency of less than or equal to eight minutes and two or more sleep onset rapid eye movement periods (SOREMPs). There is a large variability in the prevalence across different geographic

Sleep disordered breathing

Patients with sleep disordered breathing may present with sleepiness, nocturnal apneas, choking episodes, and snoring, with polysomnographic evidence of five or more apneas or hypopneas per hour. When the apneas are associated with respiratory effort, the term obstructive apnea is used, and when there is lack of respiratory effort, central apnea is used. In patients with both central and obstructive apneas, central sleep apnea is diagnosed when > 50% of the events are central.12 Patients with

REM sleep behavior disorder

REM sleep behavior disorder (RBD) is a parasomnia whereby the patient exhibits injurious or disruptive behavior in REM sleep, and is associated with increased EMG tone on submental or limb leads in REM sleep.12 Patients often lack the muscle atonia that normally accompanies REM sleep, and will act out dreams with kicking, punching, choking, and leaving the bed. RBD often takes on a violent theme, and has been reported to lead to injury of bed partners.

The overall prevalence of RBD is between

Circadian rhythm disorders

Circadian rhythm disorders (CRD) can occur from a mismatch between the internal interval and the external environment regarding the timing and duration of sleep. CRD often leads to complaints of insomnia, excessive daytime sleepiness or both, resulting in work, school, or social impairment. Patients may present with advanced sleep phase, delayed sleep phase, irregular sleep-wake rhythm or a free running sleep-wake rhythm.12

The prevalence of CRD in the general population is unknown. The

Restless legs syndrome

The restless legs syndrome (RLS), as described by Ekbom50, is a disorder with sensory and motor components. The International Restless Legs Syndrome Study Group (IRLSSG) established four clinical criteria defining RLS: 1) an urge to move, usually due to uncomfortable sensation in the legs with, 2) the urge in the legs improves with movement of the legs, 3) symptoms worsen at rest, 4) symptoms often worsen in the evening. When severe, RLS disrupts sleep, causing excessive daytime sleepiness,

Insomnia

Insomnia occurs when patients, despite adequate opportunity, have trouble with sleep initiation (initial insomnia), sleep maintenance (middle insomnia), or arising earlier than desired (terminal insomnia). According to the International Classification of Sleep Disorders-2, at least one daytime impairment symptom from insomnia must be present, including: “fatigue, mood disturbances, social and occupational problems, daytime sleepiness, loss of energy, proneness for accidents, memory impairment,

The link between cytokines, sleep and multiple sclerosis

Independent of sleep disorders, there is clear evidence that sleep and the immune system interact with each other. This interplay exists in health, in infections, and in autoimmune diseases like MS.70, 71 Cytokines are the link between sleep and the immune system. These proteins serve as chemical messengers, and help regulate sleep. The pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1), and interleukin-6 (IL-6) are the most studied cytokines in health

Sleep and medications used in MS

In addition to comorbid sleep disorders, disease modifying and symptomatic therapies commonly used in MS may also affect sleep, by causing either insomnia or hypersomnia. Those MS medications that are more commonly associated with sleep disturbances are summarized in Table 2.

Sleepiness and fatigue in MS

Fatigue is the most common symptom associated with MS. Differentiating this organic fatigue from excessive daytime sleepiness due to an underlying sleep disorder can be challenging.3, 5, *6, 85

MS fatigue is defined as a “subjective lack of physical and/or mental energy that is perceived by the individual or caregiver to interfere with usual or desired activities.” The fatigue associated with MS often occurs early in the morning, is aggravated by heat and humidity, and worsens as the day

Directions and issues for future research

While an association between MS and various sleep disorders has been established, the prevalence and strength of the associations has not yet been determined on a large-scale level. The current study limitations are due to the small numbers of subjects, selection bias, and often a lack of objective reports or polysomnographic data. Large-scale evaluations are therefore needed to define the extent to which sleep disorders affect the MS population. Further research needs to be pursued to

References* (108)

  • C. Heesen et al.

    Cognitive impairment correlates with hypothalamo-pituitary-adrenal axis dysregulation in multiple sclerosis

    Psychoneuroendocrinology

    (2002)
  • W.S. MacAllister et al.

    Multiple sclerosis-related fatigue

    Phys Med Rehabil Clin N Am

    (2005)
  • R.D. Chervin

    Sleepiness, fatigue, tiredness, and lack of energy in obstructive sleep apnea

    Chest

    (2000)
  • L.B. Strober et al.

    An examination of four models predicting fatigue in multiple sclerosis

    Arch Clin Neuropsychol

    (2005)
  • Multiple Sclerosis Society America

    Frequently asked questions [Internet]

  • N. Tachibana et al.

    Sleep problems in multiple sclerosis

    Eur Neurol

    (1994)
  • B.R. Stanton et al.

    Sleep and fatigue in multiple sclerosis

    Mult Scler

    (2006)
  • H. Kaynak et al.

    Fatigue and sleep disturbance in multiple sclerosis

    Eur J Neurol

    (2006)
  • H.P. Attarian et al.

    The relationship of sleep disturbances and fatigue in multiple sclerosis

    Arch Neurol

    (2004)
  • A.M. Bamer et al.

    Prevalence of sleep problems in individuals with multiple sclerosis

    Mult Scler

    (2008)
  • D.F. Kripke et al.

    Mortality associated with sleep duration and insomnia

    Arch Gen Psychiatry

    (2002)
  • S.R. Patel et al.

    Two epidemics: are we getting fatter as we sleep less?

    Sleep

    (2004)
  • N.T. Ayas et al.

    A prospective study of self-reported sleep duration and incident diabetes in women

    Diabetes Care

    (2003)
  • N.T. Ayas et al.

    A prospective study of sleep duration and coronary heart disease in women

    Arch Intern Med

    (2003)
  • American Academy of Sleep Medicine
  • C. Hublin et al.

    The prevalence of narcolepsy: an epidemiological study of the Finnish Twin Cohort

    Ann Neurol

    (1994)
  • K. Iseki et al.

    Hypersomnia in MS

    Neurology

    (2002)
  • O. Berg et al.

    Narcolepsy in two cases of multiple sclerosis

    Acta Neurol Scand

    (1963)
  • H. Schrader et al.

    Multiple sclerosis and narcolepsy/cataplexy in a monozygotic twin

    Neurology

    (1980)
  • D.S. Younger et al.

    Multiple sclerosis and narcolepsy: possible similar genetic susceptibility

    Neurology

    (1991)
  • G. Poirier et al.

    Clinical and sleep laboratory study of narcoleptic symptoms in multiple sclerosis

    Neurology

    (1987)
  • Y. Oka et al.

    Low CSF hypocretin-1/orexin-A associated with hypersomnia secondary to hypothalamic lesion in a case of multiple sclerosis

    J Neurol

    (2004)
  • P. Duquette et al.

    Clinical sub-groups of multiple sclerosis in relation to HLA: DR alleles as possible markers of disease progression

    Can J Neurol Sci

    (1985)
  • S.M. Caples et al.

    Obstructive sleep apnea

    Ann Intern Med

    (2005)
  • M.G. Clanet et al.

    The management of multiple sclerosis patients

    Curr Opin Neurol

    (2000)
  • Trojan DA, Da Costa D, Bar-Or A, Benedetti A, Lapierre Y, Arnold DL et al. Sleep abnormalities in multiple sclerosis...
  • Ajayi OF, Chang-McDowell T, Culpepper II WJ, Royal W, Bever CT. High prevalence of sleep disorders in veterans with...
  • I. Arnulf et al.

    Respiratory disorders during sleep in degenerative diseases of the brain stem

    Rev Neurol

    (2001)
  • R.S. Howard et al.

    Respiratory involvement in multiple sclerosis

    Brain

    (1992)
  • J.A. Stankiewicz et al.

    Acquired Ondine's curse

    Otolaryngol Head Neck Surg

    (1989)
  • J.W. Severinghaus et al.

    Ondine's curse - failure of respiratory center automaticity while awake

    Clin Res

    (1962)
  • B.A. Chaudhary et al.

    Obstructive sleep apnea after lateral medullary syndrome

    South Med J

    (1982)
  • J.J. Askenasy et al.

    Sleep apnea as a feature of bulbar stroke

    Stroke

    (1988)
  • R.N. Auer et al.

    Multiple sclerosis with medullary plaques and fatal sleep apnea (Ondine's curse)

    Clin Neuropathol

    (1996)
  • B.E. Levin et al.

    Acute failure of automatic respirations secondary to a unilateral brainstem infarct

    Ann Neurol

    (1977)
  • M.A. Nogués et al.

    Breathing control in neurological diseases

    Clin Auton Res

    (2002)
  • R.D. Chervin et al.

    Diaphragm pacing: review and reassessment

    Sleep

    (1994)
  • R.D. Chervin et al.

    Diaphragm pacing for respiratory insufficiency

    J Clin Neurophysiol

    (1997)
  • C.L. Bassetti et al.

    Sleep disordered breathing in neurologic disorders

    Swiss Med Wkly

    (2002)
  • M. Tippmann-Peikert et al.

    REM sleep behavior disorder initiated by acute brainstem multiple sclerosis

    Neurology

    (2006)
  • Cited by (0)

    The most important references are denoted by an asterisk.

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