Restless legs syndrome – Theoretical roles of inflammatory and immune mechanisms

Weinstock, Leonard B.; Walters, Arthur S.; Paueksakon, Paisit

doi:10.1016/j.smrv.2011.09.003

Cited by 138 publications

(112 citation statements)

References 213 publications

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“…35 Further, previous studies have also reported a relationship between RLS and several autoimmune diseases (e.g., MS, Crohn disease, and celiac disease). 36,37 However, we are unable to examine the association between RLS and death due to each of these disorders individually because of small numbers. When we excluded men ever reported as having major chronic conditions, such as CVD, obesity, obstructive pulmonary disease, pernicious anemia, ulcerative colitis Table 2 Risk of total mortality according to baseline restless legs syndrome status or Crohn disease, MS, and snoring every night, the association between RLS and total mortality remained significant, suggesting RLS could be a novel risk factor for total mortality, independent of these morbidities.…”

Section: Methods Study Population the Hpfs Was Established Inmentioning

confidence: 99%

Prospective study of restless legs syndrome and mortality among men

Wang

Winkelman

et al. 2013

Neurology

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Objective: To prospectively examine whether men with restless legs syndrome (RLS) had an increased risk of mortality.Method: This was a prospective cohort study of 18,425 US men free of diabetes, arthritis, and renal failure in the Health Professionals Follow-up Study (HPFS). In 2002, RLS was assessed using a set of standardized questions. Deaths were identified from state vital statistics records, the National Death Index, family reports, and the postal system.Results: During 8 years of follow-up (2002-2010), we documented 2,765 deaths. In an age-adjusted model, RLS was associated with a 39% increased risk of mortality (hazard ratio [HR] 5 1.39; 95% confidence interval [CI] 1.19-1.62; p , 0.0001). The association between RLS and mortality was slightly attenuated after further adjustment for body mass index, lifestyle factors, chronic conditions, sleep duration, and other sleep-related disorders (adjusted HR 5 1.30; 95% CI 1.11-1.52; p 5 0.003). When we further excluded those with major chronic conditions (e.g., cancer, high blood pressure, cardiovascular disease, and other comorbidities), the adjusted HR was 1.92 (95% CI 1.03-3.56; p 5 0.04). The interactions between RLS and other risk factors (older age, overweight, short sleep duration, smoking, low physical activity, and unhealthy diet) in relation to total mortality risk were not significant (p for interaction .0.2 for all). Conclusion:We observed that men with RLS had a higher overall mortality and this association was independent of known risk factors. The increased mortality in RLS was more frequently associated with respiratory disease, endocrine disease, nutritional/metabolic disease, and immunologic disorders. Future research exploring the pathophysiologic relationship between these disorders and RLS is warranted. Neurology Restless legs syndrome (RLS) is a bothersome chronic condition, characterized by an almost irresistible urge to move the legs and usually occurring with leg sensations of burning, creeping, tugging, or "like insects crawling inside the legs," which are worse in the evening and night with significant relief in the morning.1-3 This sensorimotor disorder was described in the late 17th century by Sir Thomas Willis and was coined RLS by Karl Ekbom in the 1940s.2 RLS affects 5%-10% of adults in the general population, 4-8 and is associated with various chronic conditions. 9A notable high mortality associated with RLS has been observed among men and women with renal disease. 10,11 In the general population, 3 previous studies 12-14 examined the association between RLS symptoms and mortality and reported inconsistent results. However, these studies are limited by small sample size, failure to employ standard questions to assess RLS, 12,13 or lack of information on RLS frequency.

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Section: Methods Study Population the Hpfs Was Established Inmentioning

confidence: 99%

Prospective study of restless legs syndrome and mortality among men

Wang

Winkelman

et al. 2013

Neurology

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“…A circadian fatigue in PPS may be the expression of unrecognized RLS in PPS. The frequency of RLS and PLMS is higher than general population in several neurological diseases 4,5 . The 95% of highly associated RLS conditions are linked with inflammatory/immune changes.…”

Section: Dear Editorsmentioning

confidence: 81%

Circadian variation of fatigue in paralytic poliomyelitis and postpolio syndrome: just fatigue or masked restless legs syndrome?

Romigi¹,

Placidi

Evangelista

et al. 2014

Arq. Neuro-Psiquiatr.

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“…Inflammation was most commonly associated with increased levels of proinflammatory interleukins, most commonly IL-6, but also interleukins 1, 2, 4, 12, 17, and 18. 28 Moreover, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer disease, and migraine are associated with RLS but have neither systemic nor CNS iron deficiency. 28 According to the authors, literature data raise the possibility that some of so-called idiopathic RLS could also be mediated by inflammatory and/or immunological mechanisms.…”

Section: 24mentioning

confidence: 99%

Restless Leg Syndrome in Different Types of Demyelinating Neuropathies: A Single-Center Pilot Study

Luigetti

Grande²,

Testani³

et al. 2013

Journal of Clinical Sleep Medicine

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The most common form is CMT1A, due to a duplication of a 1.4 MB region containing the gene encoding the peripheral myelin protein 22 (PMP22).9 CMT1A discloses a stereotypical sensorimotor, length-dependent neuropathy associated with marked and homogeneous slowing of nerve conduction velocities. 9 The deletion of the same chromosome 17 region causes hereditary neuropathy with liability to pressure palsy (HNPP), usually characterized by recurrent palsies due to trivial traumas. Objective: to determine the prevalence of restless legs syndrome (RLS) in a cohort of patients with demyelinating neuropathies. Methods: Patients were retrospectively recruited from our cohort of different forms of demyelinating neuropathies, including chronic infl ammatory demyelinating neuropathy (CIDP), Charcot-Marie-Tooth 1A (CMT1A), and hereditary neuropathy with liability to pressure palsies (HNPP) referred to our Department of Neurology in a 10-year period. The validated 4-item RLS questionnaire was used for diagnosis of RLS. All patients with RLS who fulfi lled criteria underwent a suggested immobilization test to confi rm the diagnosis. A group of outpatients referred to the sleep disorders unit and data from published literature were used as controls. Results: Prevalence of RLS in demyelinating neuropathy group was higher than prevalence observed in control population (p = 0.0142) or in the literature data (p = 0.0007). In particular, in comparison with both control population and literature data, prevalence of RLS was higher in CIDP group (p = 0.0266 and p = 0.0063, respectively) and in CMT1A group (p = 0.0312 and p = 0.0105, respectively), but not in HNPP (p = 1.000 and p = 0.9320, respectively). Conclusions: our study confi rms a high prevalence of RLS in infl ammatory neuropathies as CIDP and, among inherited neuropathies, in CMT1A but not in HNPP. Considering that this is only a small cohort from a single-center retrospective experience, the link between RLS and neuropathy remains uncertain, and larger multicenter studies are probably needed to clarify the real meaning of the association between RLS and neuropathy. Keywords: Restless leg syndrome (RLS), demyelinating neuropathies, chronic infl ammatory demyelinating neuropathy (CIDP), Charcot-Marie-Tooth 1A (CMT1A), hereditary neuropathy with liability to pressure palsies (HNPP), suggested immobilization test (SIT) Citation: Luigetti M; Del Grande A; Testani E; Bisogni G; Losurdo A; Giannantoni NM; Mazza S; Sabatelli M; Della Marca G. Restless leg syndrome in different types of demyelinating neuropathies: a single-center pilot study. J Clin Sleep Med 2013;9(9):945-949.

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Restless legs syndrome – Theoretical roles of inflammatory and immune mechanisms

Cited by 138 publications

References 213 publications

Prospective study of restless legs syndrome and mortality among men

Prospective study of restless legs syndrome and mortality among men

Circadian variation of fatigue in paralytic poliomyelitis and postpolio syndrome: just fatigue or masked restless legs syndrome?

Restless Leg Syndrome in Different Types of Demyelinating Neuropathies: A Single-Center Pilot Study

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