Clinical reviewRestless legs syndrome in multiple sclerosis
Introduction
Restless legs syndrome (RLS) is a sleep-related sensory-motor disorder characterized by an irresistible urge to move the legs during rest. This is usually accompanied by unpleasant sensations and discomfort of the lower extremities. The symptoms appear or increase in the evening or night and during periods of rest. Moving the legs brings total or partial relieve [1]. The essential, supportive and additional clinical features of RLS, published in 2003 by the International Restless Legs Syndrome Study Group (IRLSSG) are presented in Table 1. RLS is frequently accompanied by periodic limb movements (PLMs) which are sleep-related rhythmic, repetitive movements of the legs that may resemble the Babinski sign. PLMs are present in most RLS patients but can also be found in many other sleep and wake disorders [2].
In adults, the prevalence of symptoms of RLS vary between five and 15% and the prevalence of clinically significant RLS is between one and five percent [3]. The prevalence is higher in women and it increases with age [4], [5].
There are two forms of RLS, idiopathic and secondary RLS. In idiopathic RLS the first symptoms of RLS appear usually before the age of 50 y, while secondary RLS starts often later in life. In idiopathic RLS 40–90% of patients report a positive family history indicating a strong genetic influence [6]. Four genes have been associated with RLS in genome-wide association studies: BTBD9, MEIS1, PTPRD and MAP2KP/SCOR1. However, the possible role of these genes in determining the clinical course of RLS is unknown [7], [8], [9]. There is a strong line of evidence linking RLS to decreased iron stores in the brain. This central iron deficiency may cause disturbances in the metabolism of dopamine [10]. Disordered dopaminergic transmission is probably one of the most important components in pathophysiology of RLS, as concluded from the efficiency of dopaminergic drugs and from studies of animal models of RLS [11]. It has been postulated recently that the dopaminergic neurons located in the A11 region, which are probably the only source of dopaminergic pathways for the spinal cord, are involved in the pathology of RLS [12]. Deregulation of spinal dopaminergic transmission may lead to hyperexcitability of spinal motor and sensory pathways and cause the symptoms of RLS and PLMs [13], [14].
The conditions that cause secondary RLS include iron deficiency [15], pregnancy [16], and end-stage kidney disease [17]. The prevalence of RLS is increased in many diseases, such as neuropathies [18], primary headaches [19], myasthenia gravis [20], rheumatoid arthritis [21], celiac disease [22] or liver diseases [23].
Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system. Its etiology is not completely understood. It is characterized by appearance of relapsing or progressing focal neurological deficits. An association of MS with sleep disorders, such as narcolepsy, REM sleep behavior disorder, sleep disordered breathing or insomnia, has been described [24].
Sensory symptoms, and also symptoms of RLS are common in MS as noted for the first time by Rae-Grant and collaborators in 1999 [25]. Patients with MS describe their painful symptoms as burning, itching, electric or formicatory pain, resembling pain described by patients with RLS. Patients with MS localize their symptoms to legs and feet, trunk, arms and hands. The first epidemiological study on the occurrence of RLS in multiple sclerosis (MS) was reported by Auger et al. in 2005 [26]. Since that time numerous papers focusing on the relation between RLS and MS have been published [27], ∗[28], [29], [30], [31], [32], [33], [34], [35], [36], [37]. The aim of this review is to analyze the available data on the epidemiology and etiology of RLS in MS patients and to suggest future directions of research.
Section snippets
Epidemiological data
The prevalence of RLS in MS reported by the studies published to date ranges from 13.3% to 65.1% (Table 2). The data available from these studies are presented in Table 2. All published papers (with one exception [38]) showed that RLS is significantly more prevalent in MS patients than in the general population.
RLS in the general population is characterized by the following traits: a higher prevalence among women and in older individuals and a high prevalence of subjects with a positive family
Relationship between the clinical course of MS and RLS
In most cases, RLS develops after the diagnosis of MS. It suggests a causal relationship between demyelination and RLS symptoms. It must be remembered that the prevalence of RLS increases with age which may explain the chronology of symptom development.
MS is an autoimmunological inflammatory disease. RLS is highly prevalent in inflammatory and immunological disorders and the possible connections between inflammation and immunological alterations and development of RLS were discussed recently in
Genes or anatomy?
The studies published suggest that MS may lead to secondary RLS. The low percentage of patients with a positive family history, development of RLS after the diagnosis of MS, a higher prevalence than that of the general population and a relationship between the presence of RLS and higher scores on the EDSS suggest that RLS is secondary to MS. However, the possible pathological link between MS and RLS remains unclear.
The link between the two disorders may be of a genetic nature. For some reason,
Conflict of interests
The authors have no conflict of interests to declare.
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Restless legs syndrome in multiple sclerosis patients: Prevalence, impact, and association with disease-modifying therapies in a Saudi Arabian pilot study
2023, Multiple Sclerosis and Related DisordersRestless Legs Syndrome and fatigue in multiple sclerosis: A cross-sectional clinical study
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2022, Photodiagnosis and Photodynamic TherapyCitation Excerpt :Depending on the affected area in the central nervous system, various clinical signs and symptoms may develop, including motor, sensory, autonomic, and cognitive disorders [5]. The prevalence of RLS in MS patients is between 13.3 and 65.1%, and it is more common than in the general population with a more severe course [6–8]. Optical Coherence Tomography (OCT) is a non-invasive imaging method that uses optical back-reflection of near-infrared light views the retina, similar to histological sections [9].
Restless legs syndrome in pediatric onset multiple sclerosis
2021, Multiple Sclerosis and Related DisordersRestless legs syndrome in people with multiple sclerosis: An updated systematic review and meta-analyses
2021, Multiple Sclerosis and Related DisordersCitation Excerpt :Minár et al., 2017) Although, it has been shown that RLS appears more frequently in women, the elderly, and in people with a family history of RLS, it is still unknown if this occurs in PwMS. ( Sieminski et al., 2015) Thus, the aim of this systematic review and meta-analyses was to (i) provide updated information as to the prevalence and clinical characteristics of RLS amongst PwMS and (ii) clarify RLS-related factors in PwMS. MEDLINE (PubMed), Scopus, and EMBASE were searched from their inception through April 2021 for the following keywords used independently and in combination: ‘restless legs syndrome’ or ‘RLS’ and ‘multiple sclerosis' or ‘MS’.
Restless Legs Syndrome in Multiple Sclerosis: Risk factors and effect on sleep quality – a case-control study
2021, Multiple Sclerosis and Related DisordersCitation Excerpt :Restless Legs Syndrome (RLS) was first described in 1945 by the Swedish neurologist Karl-Axel Ekbom and is classified as an extrapyramidal hyperkinesia or, according to the German Society for Sleep Research and Sleep Medicine (DGSM), as a sleep-related movement disorder (EKBOM, 1945, S3-Leitlinie Nicht erholsamer Schlaf 2011). Moreover, there are two forms of RLS, idiopathic and secondary RLS (Sieminski et al., 2015). According to the revised diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG), RLS is characterized by a strong urge to move limbs with accompanying unpleasant sensations, worsening at rest and in the evening, improvement or complete disappearance with movement and excluded mimics (Allen et al., 2014).
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