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inflammation and disease
I've realized these last few years that my saying that I no longer have restless legs, doesn't mean anything to anyone. Scientists, doctors and RLS suffers all want the same thing - pure scientific data.

So, that's what this page is all about.

If you haven't taken a look at the web page Conditions that are Inflammation Based ... please check that out first, and then come back to this page.

The "Conditions that are Inflammation Based" page is a setup for this one. On it you'll find a collection of scientific studies confirming that ALL of the conditions listed on this page are inflammation-based.


inflammation and disease
Below you will find results from scientific studies showing that these inflammatory conditions have a significantly higher prevalence rate of Restless Legs Syndrome.

Acromegaly
Alzheimer's
Amyloidosis
Amyotrophic Lateral Sclerosis (ALS)
Anemia
Arthritis
Asthma
Ataxia
Attention Deficit Hyperactivity Disorder (ADHD)
Cancer
Celiac Disease
Chronic Obstructive Pulmonary Disease
Chronic Sarcoidosis
Chronic Venous Disorder
Crohn's Disease
Cryoglobulinemia
Depression
Diabetes
Erectile Dysfunction (ED)
Fibromyalgia
Heart Disease
Human Immunodeficiency Virus (HIV)
Irritable Bowel Syndrome
Kidney Disease / Renal Failure
Liver Disease
Lupus
Lyme Disease
Migraines
Multiple Sclerosis
Narcolepsy
Neuropathy
Obesity
Parkinson's
Poliomyelitis (Polio)
Pulmonary Hypertension
Scleroderma
Sjögren's Syndrome
Sleep Apnea
Small Intestinal Bacterial Overgrowth (SIBO)
Spinal Cord Conditions
Stroke
Tourette's Syndrome

You will also view results from scientific studies that show that pregnant women and the elderly population (two demographics that display a higher than normal amount of inflammation) also have higher rates of RLS. inflammation and disease
Restless legs syndrome (RLS), a neurological sensory-motor disorder characterized by a compelling urge to move the limbs during the night, is a sleep disturbance that impairs quality of life. Prevalence of RLS and consequences on quality of life were investigated in acromegalic patients. Fifty-six patients (20 men, 55.0 ± 1.6 years), 22 with active acromegaly (group 1) and 34 with controlled disease (group 2), and 95 controls (35 men, 52.9 ± 1.1 years) were evaluated by a structured sleep interview concerning insomnia, circadian sleep disorders and excessive diurnal sleepiness (EDS).

Our findings showed prevalence and severity of RLS is increased in patients with active acromegaly and impacts negatively on their physical performances, dramatically impairing quality of life.


"Increased prevalence of restless legs syndrome in patients with acromegaly and effects on quality of life assessed by Acro-QoL." Cannavò S, Condurso R, Ragonese M, Ferraù F, Alibrandi A, Aricò I, Romanello G, Squadrito S, Trimarchi F, Silvestri R. Pituitary. 2011 Feb 17.

inflammation and disease
The comorbidity of Attention Deficit Hyperactivity Disorder (ADHD) with sleep disorders has been extensively studied. In particular, Restless Legs Syndrome (RLS) appears to be consistently more frequent in children with ADHD.

"Restless Leg Syndrome in ADHD children: Levetiracetam as a reasonable therapeutic option." Gagliano A, Arico I, Calarese T, Condurso R, Germano E, Cedro C, Spina E, Silvestri R. Brain Dev. 2011 Jun;33(6):480-6. Epub 2010 Oct 14.

Fifty-five ADHD children (47 M, 8F; mean age=8.9 y) were included: 16 had Inattentive and 39 Hyperactive/Impulsive or Combined ADHD subtype. Behavior assessment by Conners and SNAP-IV Scales, a structured sleep interview and a nocturnal video-PSG were administered.

Most children/parents reported disturbed, fragmentary sleep at night; complaints were motor restlessness (50%), sleep walking (47.6%), night terrors (38%), confusional arousals (28.5%), snoring (21.4%), and leg discomfort at night associated with RLS (11.9%). There is a significant difference (p value <0.05 or <0.001) in almost all the studied sleep variables between ADHD children and controls. International RLS Rating Scale scoring, Periodic Limb Movements during Sleep (PLMS) and Wake (PLMW) indexes, hyperactivity and opposition scores and ADHD subtype appear related.


"Sleep disorders in children with Attention-Deficit/Hyperactivity Disorder (ADHD) recorded overnight by video-polysomnography." Silvestri R, Gagliano A, Aricò I, Calarese T, Cedro C, Bruni O, Condurso R, Germanò E, Gervasi G, Siracusano R, Vita G, Bramanti P. Sleep Med. 2009 Dec;10(10):1132-8. Epub 2009 Jun 13.

In a group of 18 children and adolescents, clinical sleep disturbance preceded a diagnosis of definite RLS by an average of 11.6 years. Many had a diagnosis of periodic limb movement disorder (PLMD) or met research criteria for probable or possible RLS prior to meeting criteria for definite RLS. These findings suggest that some aspects of RLS can occur long before full diagnostic criteria are present. Comorbidities were common, with parasomnias, ADHD, ODD, anxiety, and depression each found in more than 20% of these cases. The 2003 National Institutes of Health (NIH) diagnostic criteria for pediatric RLS are supported by this work.

"Early manifestations of restless legs syndrome in childhood and adolescence." Picchietti DL, Stevens HE. Sleep Med. 2008 Oct;9(7):770-81. Epub 2007 Nov 19.

Sleep disorders were found in 86% of ADHD children; among these, 26% had RLS. 53.1% of ADHD children had IEDs (28.2% centro-temporal spikes, 12.5% frontal spikes, 9.3% temporal-occipital spikes and 2.3% generalized S-W). Nocturnal seizures were recorded in three patients: two with atypical interictal rolandic spikes and one with left frontal slow abnormalities.

"Ictal and interictal EEG abnormalities in ADHD children recorded over night by video-polysomnography." Silvestri R, Gagliano A, Calarese T, Aricò I, Cedro C, Condurso R, Germanò E, Vita G, Tortorella G. Epilepsy Res. 2007 Jul;75(2-3):130-7. Epub 2007 Jun 27.

There could be an overlap between symptoms of ADHD and certain sleep problems such as obstructive sleep apnea syndrome, restless leg syndrome and periodic limb movements of sleep. Children undergoing evaluation for ADHD should be systematically assessed for sleep disturbances because treatment of sleep disorders is often associated with improved symptomatology and decreased need for stimulants.

"Attention deficit-hyperactivity disorder and sleep disorders". Domínguez-Ortega L, de Vicente-Colomina A. Med Clin (Barc). 2006 Apr 8;126(13):500-6.

Attention-deficit/hyperactivity disorder (ADHD) has shown associations with restless legs syndrome (RLS) and periodic leg movements during sleep (PLMS) among small samples of referred children, but whether RLS or PLMS are common more generally among hyperactive children has not been well studied.

Our study suggests that inattention and hyperactivity among general pediatric patients are associated with symptoms of PLMS and RLS.


"Associations between symptoms of inattention, hyperactivity, restless legs, and periodic leg movements." Chervin RD, Archbold KH, Dillon JE, Pituch KJ, Panahi P, Dahl RE, Guilleminault C. Sleep. 2002 Mar 15;25(2):213-8.

Sleep disruption can lead to symptoms of attention-deficit hyperactivity disorder (ADHD) in children. Since periodic limb movement disorder and/or restless legs syndrome can cause sleep disruption, we assessed whether these two specific sleep disorders are likely to occur in children with ADHD.

Eight of the 18 children with ADHD and periodic limb movement disorder and one of the two control patients with periodic limb movement disorder had both a personal and parental history of restless legs syndrome symptomatology.


"Periodic limb movement disorder and restless legs syndrome in children with attention-deficit hyperactivity disorder." Picchietti DL, England SJ, Walters AS, Willis K, Verrico T. J Child Neurol. 1998 Dec;13(12):588-94.

The occurrence and severity of current ADHD symptoms were determined in a prospective study of sequential adult patients with RLS (n = 62) or insomnia (n = 32) and adult controls (n = 77) using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) ADHD criteria, the Brown Attention-Deficit Disorder (ADD) Scale for adults, and a structured psychological interview. RLS severity was assessed using the International RLS Study Group Rating Scale (IRLS).

More RLS patients (26%) than insomnia patients (6%) or controls (5%) had ADHD symptoms using age-adjusted total DSM-IV ADHD scores (P < .01).

The results indicate that ADHD symptoms are more common in RLS patients than in patients with insomnia or controls.


"Symptoms of attention-deficit/hyperactivity disorder in adults with restless legs syndrome." Wagner ML, Walters AS, Fisher BC. Sleep. 2004 Dec 15;27(8):1499-504.

inflammation and disease
Restless legs syndrome (RLS) is characterized by disturbing leg sensations associated to sleep complaints and excessive daytime somnolence. In the elderly, it affects 10 to 35%. After testing, we conclude that RLS is a prevalent condition in elderly, may lead to sleep complaints and is often underdiagnosed.

"Restless legs syndrome in institutionalized elderly." Dantas FG, Medeiros JL, Farias KS, Ribeiro CD. Arq Neuropsiquiatr. 2008 Jun;66(2B):328-30.

The aim of this study was to evaluate and statistically describe the age-related changes in leg movements (LMs) during sleep in a large group of subjects with restless legs syndrome (RLS).

Periodic LMs during sleep (PLMS) increased in number gradually in the age groups. Their typical interval was approximately 24-28s before the age of 55years but at approximately 14-16s after the age of 65years. PLMS index reached a plateau at 15-25years of age and remained stable up to 65years; after this age, it showed an important increase.

The use of three main parameters derived from the analysis of leg motor activity during sleep in RLS patients (PLMS index, PI and PLMS time distribution) is capable of providing us with important information about the age-related changes of PLMS in this condition, which can be used in the evaluation of the sleep motor patterns in these subjects.


"Age-related changes in periodic leg movements during sleep in patients with restless legs syndrome." Ferri R, Manconi M, Lanuzza B, Cosentino FI, Bruni O, Ferini-Strambi L, Zucconi M. Sleep Med. 2008 Oct;9(7):790-8. Epub 2007 Nov 19.

Sleep disorders such as insomnia, restless leg syndrome/periodic leg movements, and obstructive sleep apnea increase in prevalence with age and are very common in persons with type 2 diabetes.

"Understanding sleep in persons with diabetes." Chasens ER. Diabetes Educ. 2007 May-Jun;33(3):435-6, 438, 441.


The prevalence of many sleep disorders increases with age. Insomnia, whether primary or secondary to coexistant illness or medication use, is very common among elderly people. Rapid eye movement (REM) sleep behaviour disorder and narcolepsy, although less common, are frequently not considered for this population. Periodic leg-movement disorder, a frequent cause of interrupted sleep, can be easily diagnosed with electromyography during nocturnal polysomnography. Restless legs syndrome, however, is diagnosed clinically.

"Sleep and aging: 1. Sleep disorders commonly found in older people." Wolkove N, Elkholy O, Baltzan M, Palayew M. CMAJ. 2007 Apr 24;176(9):1299-304.

Insomnia affects 20% of the adult population in western countries and its prevalence increases with age. There is a controversy regarding the origin of sleep disorders in elderly. Are they only due to a senile process of sleep functioning or due to other associated comorbidities? Considering the objective assessment of sleep in elderly (by polysomnography), it has been shown an increasing sleep latency, decreasing total sleep time and sleep efficiency, a lower percentage of slow wave sleep. The circadian clock is also modified by age with phase advance and a decreased amplitude of the circadian rhythms.

The most relevant comorbidities found in older people are: sleep apneas, restless leg syndrome, psychiatric disorders (anxiety and depression) and the use of drugs.


"Sleep disorders in elderly." Corman B, Léger D. Rev Prat. 2004 Jun 30;54(12):1281-5.

One hundred unrelated patients diagnosed with primary RLS were studied. During wakefulness, frequency of PLM increased and the mean inter-movement interval decreased with advancing age. The modal value of inter-movement interval distribution was also altered suggesting that aging influences rhythm-generation mechanisms.

"The influence of sex, age and sleep/wake state on characteristics of periodic leg movements in restless legs syndrome patients." Nicolas A, Michaud M, Lavigne G, Montplaisir J. Clin Neurophysiol. 1999 Jul;110(7):1168-74.

inflammation and disease
Normal sleep is important for health and mental wellness. Unfortunately, pathological changes associated with Alzheimer’s disease increase the risk of sleep disturbances in these patients. Indeed a large number of patients with AD suffer from a variety of sleep disorders. These disturbances result in daytime sleepiness and can also further impair mood and cognition. As a result, the condition of Alzheimer’s patients can decline and lead to increased burden and exhaustion for care givers.

Certain specific sleep disorders are far more common in patients with Alzheimer’s. These can include: sleep apnea, restless legs, altered sleep-wake cycle, and abnormal movements during sleep.


"Recognition and Improving Sleep Problems in Alzheimer’s: General Guidelines for Caregivers." Mansoor Ahmed M.D., F.C.C.P., F.A.A.S.M. Cleveland Sleep Research Center (2011).

Sleep in dementias has been mainly studied in Alzheimer disease (AD). Sleep disturbances are found in 25 to 35% of subjects with AD. Sleep-disordered breathing is a highly prevalent condition in AD patients and restless leg syndrome may account for nocturnal agitation. In Parkinson and in Lewy body dementias, sleep disturbances are more severe than in DA and REM sleep behavior disorder can precede by several years these diseases.

"Sleep disturbances in Alzheimer's disease and other dementias." Vecchierini MF. Psychol Neuropsychiatr Vieil. 2010 Mar;8(1):15-23.

Scientists do not completely understand why sleep disturbances occur in people with dementia. Sleep disturbances associated with Alzheimer’s disease include increased frequency and duration of awakenings, decrease in both dreaming and nondreaming stages of sleep, and daytime napping. Similar changes occur in the sleep of older people who do not have dementia, but these changes occur more frequently and tend to be more severe in people with Alzheimer’s disease.

Coexisting conditions may intensify sleep problems for older adults with Alzheimer’s. Two conditions in which involuntary movements interfere with sleep are periodic limb movement and restless leg syndrome. Other common conditions that disrupt sleep include nightmares and sleep apnea, an abnormal breathing pattern in which people briefly stop breathing many times a night. Depression in a person with dementia may further worsen sleep difficulties.


"Sleep changes in Alzheimer’s disease." Alzheimer’s Association. 2006. www.alzdsw.org

Myoclonus is brief, involuntary twitching of a muscle or a group of muscles. The myoclonic twitches are usually caused by sudden muscle contractions; they also can result from brief lapses of contraction. The most common time for people to encounter them is while falling asleep (hypnic jerk), but myoclonic jerks are also a sign of a number of neurological disorders.

Myoclonic jerks may occur alone or in sequence, in a pattern or without pattern. They may occur infrequently or many times each minute. Most often, myoclonus is one of several signs in a wide variety of nervous system disorders such as multiple sclerosis, Parkinson's disease, Alzheimer's disease, subacute sclerosing panencephalitis and Creutzfeldt-Jakob disease (CJD).


"Myoclonus." Wikipedia en.wikipedia.org/wiki/Myoclonus

A clinically relevant sleep-wake disturbance is found in up to half the patients with dementia, and the sundowning agitation is a common cause of institutionalisation of demented geriatric patients.

The circadian rhythm of demented patients is levelled off with increased daytime sleep and disrupted night sleep. Particularly in vascular dementia, Korsakow syndrome, Parkinson's disease, and depression the alteration of sleep architecture may be pronounced, whereas in Alzheimer's disease prominent hypersomnolence or insomnia is typically only found in later stages of the diseases.


"Sleep disorders and dementia." Hess CW. Praxis (Bern 1994). 1997 Aug 27;86(35):1343-9.

inflammation and disease
Restless legs syndrome was the first isolated clinical manifestation in four siblings of a family with familial amyloid polyneuropathy.

"Restless legs syndrome and nocturnal myoclonus: initial clinical manifestation of familial amyloid polyneuropathy." F Salvi, P Montagna, R Plasmati, G Rubboli, F Cirignotta, M Veilleux, E Lugaresi and C A Tassinari. J Neurol Neurosurg Psychiatry. 1990 June; 53(6): 522–525.

Primary amyloidosis is a multisystem disease which may present in myriad ways such as congestive heart failure, purpura, gastrointestinal disturbances, and nephrotic syndrome. Involvement of the autonomic and peripheral nervous system may also occur. A case of primary amyloidosis is reported in which severe orthostatic hypotension and the restless leg syndrome were the initial manifestations.

"Restless Legs and Orthostatic Hypotension in Primary Amyloidosis." E. G. Heinze, Jr., MD; Boy Frame, MD; G. Fine, MD. Arch Neurol. 1967;16(5):497-500.

inflammation and disease
Abstract Restless legs syndrome (RLS) appears to be more frequent in certain neurodegenerative disorders. The aim of our study was to determine the frequency and the determinants of the association of RLS with amyotrophic lateral sclerosis (ALS) in a French cohort. Information on sex, age, age at onset, site of onset, body mass index, disease duration, ALS Functional Rating Scale-Revised and use of technical supports was obtained in a cohort of 69 ALS subjects (69.6 ± 9.7 years).

RLS was observed in 13 patients (18.8%). Frequency of RLS was higher (p = 0.007) in ALS patients older than 64 years than in the French general population of the same age group. There were no further demographic, clinical or biological differences between the patients with RLS and those without RLS, with the exception of a higher frequency of difficulty turning in bed and adjusting bedclothes (p = 0.023). In conclusion, RLS occurs frequently in ALS, and those affected should be identified and appropriately treated.


"The high frequency of restless legs syndrome in patients with amyotrophic lateral sclerosis." Limousin N, Blasco H, Corcia P, Arnulf I, Praline J. Amyotroph Lateral Scler. 2011 Feb 11.

We aimed to evaluate the frequency and determinants of restless legs syndrome (RLS) in a group of 76 patients with amyotrophic lateral sclerosis (ALS) and 100 control subjects.

RLS was significantly more frequent in patients with ALS (ALS/RLS(+)) than in control subjects (25% vs. 8%; P = 0.002). Compared with control subjects, patients with ALS/RLS(+) showed shorter history of RLS complaints and higher frequency of symptoms occurrence. Moreover, compared with those without RLS, patients with ALS/RLS(+) showed increased functional impairment and more often reported sleep complaints. Multivariate logistic regression confirmed the association between RLS and functional impairment.

Our findings suggest that RLS should be considered as a possible cause of disrupted sleep in patients with ALS and should be specifically investigated in these patients.


"Restless legs syndrome in patients with amyotrophic lateral sclerosis." Lo Coco D, Piccoli F, La Bella V. Mov Disord. 2010 Nov 15;25(15):2658-61.

inflammation and disease
Iron deficiency is associated with paediatric sleep disturbances; in particular, restless leg syndrome (RLS) and periodic limb movement disorder (PLMD). Correction of iron deficiency has been shown to improve sleep disordered breathing (SDB) in certain adult populations.

"Iron deficiency and sleep disordered breathing in children--cause or effect?" Kerstein R, Stimpson P, Caulfield H, Ellis G. Int J Pediatr Otorhinolaryngol. 2009 Feb;73(2):275-80. Epub 2008 Dec 10.

Association of iron deficiency with febrile seizures, pica, breath holding spells, restless leg syndrome and thrombosis is increasingly being recognized.

"Iron deficiency: beyond anemia." Yadav D, Chandra J. Indian J Pediatr. 2011 Jan;78(1):65-72. Epub 2010 Sep 3.

The pathogenesis of restless legs syndrome (RLS) is unknown. Although iron deficiency anemia (IDA) is related with RLS, the mechanism of this relationship is still unknown.

"Iron deficiency anemia and restless legs syndrome: is there an electrophysiological abnormality?" Akyol A, Kiylioglu N, Kadikoylu G, Bolaman AZ, Ozgel N. Clin Neurol Neurosurg. 2003 Dec;106(1):23-7.

inflammation and disease
The prevalence of the restless leg syndrome among patients with rheumatoid arthritis in hospital is high (30%) and significantly different from that among normal controls and patients with osteoarthritis. Immobility per se does not seem to be a primary factor as the patients with osteoarthritis did not show an increased prevalence compared with the control group.

The combination of the restless leg syndrome and rheumatoid arthritis contributes considerably to discomfort and anxiety, and in our experience few doctors are aware of this condition.


"Restless leg syndrome and rheumatoid arthritis." G Reynolds, D R Blake, H S Pall, and A Williams. Br Med J (Clin Res Ed). 1986 March 8; 292(6521): 659–660.

Since RLS is common in rheumatologic disorders such as rheumatoid arthritis or Sjögren's syndrome, rheumatologists need to be familiar with the condition. Primary care physicians may misattribute RLS symptoms to other conditions and refer patients to specialists for treatment. Since RLS symptoms can be similar to, and mistaken for, symptoms in rheumatologic diseases, patients may be referred to rheumatologists. Therefore, it is important that rheumatologists be able to recognize, differentiate, diagnose, and treat RLS.

"Restless legs syndrome: a common disorder in patients with rheumatologic conditions." Hening WA, Caivano CK. Semin Arthritis Rheum. 2008 Aug;38(1):55-62. Epub 2007 Oct 30.

Our study shows an association between fibromyalgia syndrome and restless legs syndrome as well as leg cramps and confirms a previously reported association between rheumatoid arthritis and restless legs. The basis of this association is not clear. Fibromyalgia is not a psychiatric condition, and we found no association between restless legs syndrome and psychological state.

"Restless legs syndrome and leg cramps in fibromyalgia syndrome: a controlled study." Muhammad BYunus, Jean C Aldag, BMJ vol 312 25 May 1996

inflammation and disease
Current medication use was obtained from 110 RLS patients and 54 age, race and gender-matched local-community controls. Each subject was diagnosed as primary RLS or having no indications for RLS by a clinician board-certified in sleep medicine. The RLS group used more medications than the control group even when medications used for treating RLS were excluded.

Significantly more of the RLS patients than controls used anti-depressants, gastro-intestinal (GI) medications and asthma/allergy medications.


"Medication use in patients with restless legs syndrome compared with a control population." Pearson VE, Gamaldo CE, Allen RP, Lesage S, Hening WA, Earley CJ. Eur J Neurol. 2008 Jan;15(1):16-21. Epub 2007 Nov 14.

inflammation and disease
We recruited 40 patients with clinical and molecular-proven SCA3/MJD and 38 controls. We used the following clinical scales to evaluate our primary outcome measures: RBD Screening Questionnaire, International RLS Rating Scale, and Epworth Sleepiness Scale. To evaluate ataxia-related motor and non-motor features, we applied the International Cooperative Ataxia Rating Scale, the Scale for the Assessment and Rating of Ataxia, and the Unified Parkinson's Disease Rating Scale part III. Psychiatric manifestations were tested with the Hamilton Anxiety Scale, and Beck Depression Inventory.

The frequency of RBD and RLS were significantly higher in the SCA3/MJD group than in the control group (p < 0.001).


"Sleep Disorders in Machado-Joseph Disease: Frequency, Discriminative Thresholds, Predictive Values, and Correlation with Ataxia-Related Motor and Non-Motor Features." Pedroso JL, Braga-Neto P, Felício AC, Dutra LA, Santos WA, do Prado GF, Barsottini OG. Cerebellum. 2011 Feb 2.

Friedreich ataxia (FA) is the most common type of hereditary ataxia. Frataxin deficiency due to a GAA expansion in the first intron of chromosome 9 results in intramitochondrial iron accumulation. On the basis of the patients' complaints about sleep disturbance and pathophysiological considerations, we systematically assessed sleep history and polysomnography in FA.

We included 16 consecutive FA patients (11 men, 5 women; mean age, 35.4 ± 11.1 years) with a mean disease duration of 16.5 ± 7.0 years. All patients underwent a standardized protocol including a detailed sleep history and polysomnographic recordings.

Eight out of 16 patients were diagnosed with restless legs syndrome (RLS). In seven patients, RLS onset was after the onset of FA. Interestingly, FA patients with RLS had significantly lower serum ferritin levels than FA patients without RLS (76.3 ± 56.0 ?g/L vs. 176.3 ± 100.7 ?g/L; P = 0.043 after correction for sex and age). Moreover, periodic leg movements in wakefulness (PLMW) indices were significantly higher in FA patients with RLS than FA patients without RLS (FA with RLS, 118.1 ± 50.7; FA without RLS, 65.6 ± 44.2; P = 0.028).


"Restless legs syndrome in Friedreich ataxia: A polysomnographic study." Frauscher B, Hering S, Högl B, Gschliesser V, Ulmer H, Poewe W, Boesch SM. Mov Disord. 2010 Dec 13.

Patients with MJD/SCA3 reported more symptoms of insomnia, restless leg syndrome and REM sleep behavior disorder as well as nocturnal cramps, snoring and nocturnal apnea.

"Sleep symptoms and their clinical correlates in Machado-Joseph disease." D'Abreu A, França M Jr, Conz L, Friedman JH, Nucci AM, Cendes F, Lopes-Cendes I. Acta Neurol Scand. 2009 Apr;119(4):277-80. Epub 2008 Sep 3.

Two out of five patients fulfilled the clinical criteria for RLS. A periodic leg movements in sleep (PLMS) index>15/h was present in four of the five patients; a PLMS index>5/h was present in all patients. Significant disturbance of rapid eye movement (REM) sleep was not found. None of the patients had REM sleep behaviour disorder. Only one patient had mild REM sleep without atonia.

"Restless legs syndrome and motor activity during sleep in spinocerebellar ataxia type 6." Boesch SM, Frauscher B, Brandauer E, Wenning GK, Poewe W, Hogl B. Sleep Med. 2006 Sep;7(6):529-32. Epub 2006 Aug 23.

The high prevalence of RLS in FA patients warrants specific assessment by neurologists involved in the care of FA patients as treatments are readily available. Similar to patients with idiopathic RLS, reduced SN echogenicity is a frequent finding in FA, possibly indicating regional changes in subcellular brain iron regulation in FA.

"Restless legs and substantia nigra hypoechogenicity are common features in Friedreich's ataxia." Synofzik M, Godau J, Lindig T, Schöls L, Berg D. Cerebellum. 2011 Mar;10(1):9-13.

inflammation and disease
RLS was present in 47 patients (18.3%), 14 males (11.8%) and 33 females (23.9%); (p=0.01). RLS directly correlated with pain (p<0.0001), nausea (p<0.001), worse physical well-being (p=0.007), emotional well- being (p=0.001) and functional well-being (p=0.02). RLS affected patients showed higher levels of anxiety (p<0.001) and depression (p=0.001). The styles of coping consisting in anxious preoccupation and hopeless were also more represented in the RLS affected patients (p=0.04 and p=0.02 respectively) than their counterparts.

Our results show that RLS is frequent and underdiagnosed in cancer patients. It may cause anxiety, depression and quality of life deterioration. Early RLS detection and prompt introduction of dopamine agonists may improve patient quality of life.


"High prevalence of restless legs syndrome in cancer patients undergoing chemotherapy: Relationship with anxiety, depression and quality of life perception." A. Saini, L. Ostacoli, E. Sguazzotti, S. Capogna, C. Castronovo, V. Dongiovanni, G. Gorzegno, P. M. Furlan, L. Dogliotti, A. Berruti. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 9032

The prevalence of RLS in cancer patients undergoing chemotherapy is 18.3%, about double of that expected in the general population. The occurrence of RLS is much more frequent in female patients and with longer-term chemotherapy. Cancer patients afflicted by RLS have significantly higher levels of anxiety and depression, and poorer quality of life especially in the physical well-being dimension. Recognition and treatment of RLS in cancer patients is an important target in clinical management and may improve quality of life and overall health outcomes in these patients.

"Restless legs syndrome and its relationship with anxiety, depression, and quality of life in cancer patients undergoing chemotherapy." Ostacoli L, Saini A, Ferini-Strambi L, Castronovo V, Sguazzotti E, Picci RL, Toje M, Gorzegno G, Capogna S, Dongiovanni V, Dogliotti L, Furlan PM, Berruti A. Qual Life Res. 2010 May;19(4):531-7. Epub 2010 Feb 27.

Sleep difficulty is a prominent concern of cancer patients, yet there has been no large study of the prevalence and nature of sleep disturbance in cancer patients. This cross-sectional survey study examined: (a) the prevalence of reported sleep problems in patients attending six clinics at a regional cancer centre; (b) sleep problem prevalence in relation to cancer treatment; and (c) the nature of reported insomnia (type, duration, and associated factors). For three months, all patients attending clinics for breast, gastrointestinal, genitourinary, gynecologic, lung, and non-melanoma skin cancers were offered a brief sleep questionnaire. Response rate was 87%; the final sample size was 982. Mean age of respondents was 64.9 years (SD 12.5). The most prevalent problems were excessive fatigue (44% of patients), leg restlessness (41%). insomnia (31%), and excessive sleepiness (28%).

"Sleep disturbance in cancer patients." Davidson JR, MacLean AW, Brundage MD, Schulze K. Soc Sci Med. 2002 May;54(9):1309-21.

inflammation and disease
Celiac disease may be associated with restless legs syndrome (RLS) because of an association with iron deficiency. Often, RLS negatively affects quality of life but may remain undiagnosed. This study evaluated the association between celiac disease and RLS.

The incidence of RLS among 85 patients with celiac disease was 35%, with a prevalence of 25% compared with 10% of spouses (P<0.02). In 79% of patients with RLS and celiac disease, neuromuscular symptoms began during or after onset of gastrointestinal symptoms. Iron deficiency was present in 40% of celiac patients with active RLS compared with 6% of patients without RLS (P<0.001). After 6 months of a gluten-free diet, RLS symptoms improved in 50% of 28 patients.

Screening for celiac disease in patients with RLS is important since this commonly overlooked silent disease may be a correctable factor for some patients with idiopathic RLS.


"Celiac disease is associated with restless legs syndrome." Weinstock LB, Walters AS, Mullin GE, Duntley SP. Dig Dis Sci. 2010 Jun;55(6):1667-73.

The association of RLS and celiac disease may be underestimated. Our patient presented with a simultaneous exacerbation of RLS, abdominal pain and diarrhea. Substantial improvement of her symptoms was achieved by iron supplementation and a gluten-free diet. Iron deficiency or an unknown immune mechanism could explain the association of these two diseases.

"Restless leg syndrome in a patient with celiac disease: a coincidence or an association?" Fady G. Haddad, Georges D. Maalouly, Joe I. Fahed, Mouin H. Jammal, and Rita J. El NemnoumAnn Saudi Med. 2009 May-Jun; 29(3): 239. Ann Saudi Med. 2009 May-Jun; 29(3): 239. doi: 10.4103/0256-4947.51779.

We investigated RLS prevalence in celiac disease (CD), an autoimmune disease characterized by several features such as malabsorption-related iron deficiency anemia and peripheral neuropathy.

We found a 31% prevalence of RLS in the CD population that was significantly higher than the prevalence in the control population (4%; P < 0.001).


"Restless legs syndrome is a common feature of adult celiac disease." Moccia M, Pellecchia MT, Erro R, Zingone F, Marelli S, Barone DG, Ciacci C, Strambi LF, Barone P. Mov Disord. 2010 May 15;25(7):877-81.

inflammation and disease
Despite complaints of poor sleep being very common in people with chronic obstructive pulmonary disease (COPD), restless legs syndrome (RLS) symptoms have not been extensively investigated in these patients.

A total of 87 patients with COPD and 110 controls, matched for age and sex, were evaluated regarding the presence and severity of RLS symptoms.

RLS was significantly more frequent in COPD patients than in controls (36.8% vs. 11%; p < 0.001).

RLS is a frequent cause of disabling sleep disturbance in patients with COPD and should be specifically investigated in these patients.


"Increased frequency of restless legs syndrome in chronic obstructive pulmonary disease patients." Lo Coco D, Mattaliano A, Lo Coco A, Randisi B. Sleep Med. 2009 May;10(5):572-6. Epub 2008 Nov 8.

Our objective is to evaluate the prevalence of restless legs syndrome (RLS) in patients with chronic obstructive pulmonary disease (COPD) and the relationship between RLS and clinical/laboratory findings of COPD.

One hundred and thirty-four COPD patients without secondary causes of RLS were included. Thirty-nine (29.1%) patients were diagnosed with RLS and classified as Group 1. The control group consisted of 65 age-matched COPD patients without RLS. Group 1 was divided into subgroups according to the Johns Hopkins Severity (JHS) scale. Patients with a score of 0, 1, or 2 were classified as JHS 0-2 and those with a score of 3 as JHS 3. Group 1 and the control group and subgroups were compared for clinical and laboratory characteristics.

We found that the duration of COPD was longer and that airway obstruction, hypercapnia, and hypoxia were more evident in patients with RLS than those without.

We conclude that RLS is frequent in COPD, particularly in patients with severe hypoxemia/hypercapnia and in late stages of the disease.


"Restless legs syndrome in patients with chronic obstructive pulmonary disease." Kaplan Y, Inonu H, Yilmaz A, Ocal S. Can J Neurol Sci. 2008 Jul;35(3):352-7.

Chronic obstructive pulmonary disease (COPD) is a prevalent progressive condition that adversely affects quality of life and sleep. Patients with COPD suffer from variety of sleep disorders including insomnia, sleep disordered breathing and restless leg syndrome.

"Sleep disorders and their management in patients with COPD." Sharafkhaneh A, Jayaraman G, Kaleekal T, Sharafkhaneh H, Hirshkowitz M. Ther Adv Respir Dis. 2009 Dec;3(6):309-18. Epub 2009 Oct 30.

inflammation and disease
Many sarcoidosis patients suffer from fatigue and sleep disturbances. Recently, it was demonstrated that obstructive sleep apnea (OSA) is rather common in sarcoidosis. Moreover, sheet intolerance and painful legs are frequently reported in sarcoidosis patients. These symptoms might interfere with sleep quality.

Sleep disturbance (OSA and/or PLM) and RLS were demonstrated in more than half of the studied sarcoidosis patients.


"Sleep disturbances associated with periodic leg movements in chronic sarcoidosis." Verbraecken J, Hoitsma E, van der Grinten CP, Cobben NA, Wouters EF, Drent M. Sarcoidosis Vasc Diffuse Lung Dis. 2004 Jun;21(2):137-46.

inflammation and disease
Of the 174 consecutive subjects studied (22M: 152F), 63 (36%) had evidence of RLS compared with only 34 of 174 of the controls (19%, P < 0.05). Sixty-two (98%) of these RLS-positive study subjects were subsequently diagnosed with CVD. In comparison, 31 (91%) of the RLS-positive control subjects (n = 34) were found to have CVD. This prevalence of CVD was comparable with RLS-positive study subjects, but was significantly higher than the prevalence in CVD in RLS-negative controls (P < 0.01). Only three (9%) of the controls had RLS without CVD. RLS-positive subjects were typically women above the age of 40 years (P < 0.01 vs. men, P < 0.01 vs. below 40 years).

RLS appears to be a common overlapping clinical syndrome in patients with CVD.


"Restless legs syndrome in patients with chronic venous disorders: an untold story." McDonagh B, King T, Guptan RC. Phlebology. 2007;22(4):156-63.

inflammation and disease
Extraintestinal manifestations of Crohn's disease (CD) have not previously included the central nervous system (CNS). Restless legs syndrome (RLS) is a CNS disorder that is either idiopathic or secondary to a number of diseases. The aim of this study was to determine if RLS was associated with CD because both are associated with iron deficiency, inflammation, and bacterial overgrowth.

Consecutive CD outpatients (N = 272) were prospectively surveyed at 4 centers for criteria for RLS. Incidence (having RLS at any point in time), prevalence (having RLS at time of survey), clinical characteristics, risk factors, and potential qualitative relationship between RLS and gastrointestinal symptoms were queried.

The incidence of RLS in patients with CD was 42.7%. Prevalence was 30.2% compared with 9% of spouses. CD patients with and without RLS had a mean age of 46.8 versus 42.6 years, small intestine involvement in 77.9% versus 66.7%, colon involvement in 39.7% versus 63.2%, and prior iron deficiency anemia in 49.3% versus 33.1%. There was no difference between the CD groups with respect to current iron deficiency, RLS family history, or rare prevalence of concomitant RLS disorders. In 91.8% of patients with RLS and CD, RLS started during or after the onset of CD diagnosis. Among 73 patients with RLS, 67 (44.5%) stated there was a relationship between qualitative RLS symptom improvement with overall CD symptom improvement.

These results demonstrate that RLS occurs frequently in CD and appears to be a possible extraintestinal manifestation. The potential relationship of RLS with CD activity warrants further investigation.


"Crohn's disease is associated with restless legs syndrome." Weinstock LB, Bosworth BP, Scherl EJ, Li E, Iroku U, Munsell MA, Mullen GE, Walters AS. Inflamm Bowel Dis. 2010 Feb;16(2):275-9.

inflammation and disease
The most important finding of our review is that symptoms of depression are common in individuals with RLS. The association between RLS and depression symptoms is likely a complex one. Because the epidemiologic studies supporting this association are cross-sectional and thus correlational, possible explanations for the observed association between these two include: RLS causes depression, depression causes RLS, or a third factor causes both RLS and depression.

"Restless Legs Syndrome, Periodic Limb Movements in Sleep, and Depression." Daniel Picchietti, MD1; John W. Winkelman, MD, PhD. SLEEP, Vol. 28, No. 7, 2005

The authors examined the association between restless legs syndrome (RLS) and DSM-IV major depressive disorder and panic disorder based on Wave III and IV of the Baltimore ECA follow-up study. Of 1071 participants, 1024 completed the RLS Questionnaire and Diagnostic Interview Schedule.

Lifetime prevalence of any psychiatric disorders was 36.8% (n=14) among participants with restless legs syndrome and was substantially higher than in participants without restless legs syndrome (14.6%, n=129). Among the psychiatric diagnoses, DSM-IV major depressive disorder was the most common diagnosis with a lifetime and 12-month prevalence of 19.0% (n=8) and 9.5% (n=4) among participants with restless legs syndrome.


"Restless Legs Syndrome is Associated with DSM-IV Major Depressive Disorder and Panic Disorder in the Community." Hochang B. Lee, M.D., Wayne A. Hening, M.D, Ph.D., Richard P. Allen, Ph.D., Amanda E. Kalaydjian, Ph.D., Christopher J. Earley, M.B.B.Ch., Ph.D., William W. Eaton, Ph.D. and Constantine G. Lyketsos, M.D., M.H.S. J Neuropsychiatry Clin Neurosci 20:101-105, February 2008 doi: 10.1176/appi.neuropsych.20.1.101

Symptoms of depression are very common in adults with RLS. Approximately 40% of people with RLS complain of symptoms that would be indicative of depression if assessed without knowledge or consideration of the sleep disorder.

"Restless legs syndrome, periodic limb movements in sleep, and depression." Picchietti D, Winkelman JW. Sleep 2005; 28(7):891-8.

"Anxietas Tibiarum Depression and anxiety disorders in patients with restless legs syndrome." Winkelmann J, Prager M, Lieb R, et al. J Neurol 2005; 252:67-71.

"Correlation of anxiety and depression symptoms in patients with restless legs syndrome: a population based survey." Sevim S, Dogu O, Kaleagasi H,Aral M, Metin O, Camdeviren H. J Neurol Neurosurg Psychiatry 2004; 75:226-30.

"Sleep disorders and depressive feelings: a global survey with the Beck depression scale." Vandeputte M, de Weerd A. Sleep Med 2003; 4:343-5.

"Prevalence and risk factors of RLS in an elderly population: the MEMO study." Rothdach AJ, Trenkwalder C, Haberstock J, Keil U, Berger K. Memory and Morbidity in Augsburg Elderly. Neurology 2000; 54:1064-8.

"Restless legs syndrome in 218 patients: associated disorders." Banno K, Delaive K, Walld R, Kryger MH. Sleep Med 2000; 1:221-9.


Significantly greater anxiety and depression symptoms were observed among patients with RLS than in the control subjects. Our data also seem to provide initial evidence of a correlation between the severity of RLS and of anxiety and depression symptoms (r = 0.21, p = 0.03 and r = 0.201, p = 0.04 respectively).

"Correlation of anxiety and depression symptoms in patients with restless legs syndrome: a population based survey." Sevim S, Dogu O, Kaleagasi H,Aral M, Metin O, Camdeviren H. J Neurol Neurosurg Psychiatry 2004; 75:226-30.

Current medication use was obtained from 110 RLS patients and 54 age, race and gender-matched local-community controls. Each subject was diagnosed as primary RLS or having no indications for RLS by a clinician board-certified in sleep medicine. The RLS group used more medications than the control group even when medications used for treating RLS were excluded.

Significantly more of the RLS patients than controls used anti-depressants, gastro-intestinal (GI) medications and asthma/allergy medications.


"Medication use in patients with restless legs syndrome compared with a control population." Pearson VE, Gamaldo CE, Allen RP, Lesage S, Hening WA, Earley CJ. Eur J Neurol. 2008 Jan;15(1):16-21. Epub 2007 Nov 14.

inflammation and disease
There is a higher incidence of restless legs syndrome (Ekbom's syndrome) in patients after gastric surgery (11·3%) and with diabetes mellitus (17·0%) and uraemia (17·3%) than in patients who have been diagnosed as having a psychonoeurosis (4·0%) and in controls (2·0%). The incidence after gastric surgery and in diabetes mellitus and uraemia remained high even when patients with any abnormal neurological signs were excluded.


"Restless Legs Syndrome, with Particular Reference to its Occurrence After Gastric Surgery." N. K. Banerji and L. J. Hurwitz. Br Med J. 1970 December 26; 4(5738): 774–775.

RLS is a serious and not uncommon problem among patients with diabetes mellitus. This syndrome is closely related to diabetic neuropathy and probably to metabolic factors in its pathogenesis. Diagnosis of RLS is often delayed and because it can be effectively treated, a better education of the general medical community toward greater awareness of the syndrome is necessary.

"Clinical characteristics and associated comorbidities in diabetic patients with restless legs syndrome." Greco D, Gambina F, Pisciotta M, Abrignani M, Maggio F. Exp Clin Endocrinol Diabetes. 2009 Oct;117(9):496-9. Epub 2009 Jun 17.

Before people develop type 2 diabetes, they almost always have "prediabetes"—blood glucose levels that are higher than normal but not yet high enough to be diagnosed as diabetes. There are 79 million people in the United States who have prediabetes.

Our study suggests that IGT (prediabetes) is frequently associated with idiopathic RLS.


"Prediabetes." American Diabetes Association www.diabetes.org/diabetes-basics/prevention/pre-diabetes

"Role of the Oral Glucose Tolerance Test (OGTT) in the idiopathic restless legs syndrome." Bosco D, Plastino M, Fava A, Ettore M, Bosco F, Ermio C, Tallarigo F, Pirritano D, Consoli D. J Neurol Sci. 2009 Dec 15;287(1-2):60-3. Epub 2009 Sep 26.

"Age-related changes in periodic leg movements during sleep in patients with restless legs syndrome." Ferri R, Manconi M, Lanuzza B, Cosentino FI, Bruni O, Ferini-Strambi L, Zucconi M. Sleep Med. 2008 Oct;9(7):790-8. Epub 2007 Nov 19.


Sleep disorders such as insomnia, restless leg syndrome/periodic leg movements, and obstructive sleep apnea increase in prevalence with age and are very common in persons with type 2 diabetes.

"Understanding sleep in persons with diabetes." Chasens ER. Diabetes Educ. 2007 May-Jun;33(3):435-6, 438, 441.

The aim of this study was to assess the prevalence of RLS in a cohort of patients with diabetic neuropathy and to analyze the features of the associated neuropathy.

Our data show that RLS is a relevant feature of diabetic neuropathy, as a frequent and potentially treatable manifestation of small fiber involvement in the course of DM and IGT/IFG.


"Restless legs syndrome in diabetic neuropathy: a frequent manifestation of small fiber neuropathy." Gemignani F, Brindani F, Vitetta F, Marbini A, Calzetti S. J Peripher Nerv Syst. 2007 Mar;12(1):50-3.

inflammation and disease
Dopaminergic hypofunction in the central nervous system may contribute to restless legs syndrome (RLS) and erectile dysfunction (ED). We therefore examined whether men with RLS have higher prevalences of ED.

Multivariate-adjusted odds ratios for ED were 1.16 and 1.78 (95% confidence interval: 1.4, 2.3; P trend < 0.0001) for men with RLS symptoms 5-14 times/mo, and 15+ times/mo, respectively, relative to those without RLS, after adjusting for age, smoking, BMI, antidepressant use, and other covariates.

Men with RLS had a higher likelihood of concurrent ED, and the magnitude of the observed association was increased with a higher frequency of RLS symptoms. These results suggest that ED and RLS share common determinants.


"Restless legs syndrome and erectile dysfunction." Gao X, Schwarzschild MA, O'Reilly EJ, Wang H, Ascherio A. Sleep. 2010 Jan;33(1):75-9.

inflammation and disease
Our study shows an association between fibromyalgia syndrome and restless legs syndrome as well as leg cramps and confirms a previously reported association between rheumatoid arthritis and restless legs. The basis of this association is not clear. Fibromyalgia is not a psychiatric condition, and we found no association between restless legs syndrome and psychological state.

"Restless legs syndrome and leg cramps in fibromyalgia syndrome: a controlled study." Muhammad BYunus, Jean C Aldag BMJ vol 312 25 May 1996

"Fibromyalgia, restless legs syndrome, periodic limb movement disorder and psychogenic pain." Yunus MB, Masi AT. In: McCarty DJ, Koopman WJ, eds. Arthritis and aUied conditions: a textbook of rheumatology. 12th ed. Philadelphia: Lea and Febiger, 1993:1383-1405.

"Restless legs syndrome and rheumatoid arthritis." Reynolds G, Blake DR, Hall HS, Williams A. R BMJ 1986;292:659-60.


Disordered sleep is such a prominent symptom in fibromyalgia that the American College of Rheumatology included symptoms such as waking unrefreshed, fatigue, tiredness, and insomnia in the 2010 diagnostic criteria for fibromyalgia. Even though sleep recording is not part of the routine evaluation, polysomnography may disclose primary sleep disorders in patients with fibromyalgia, including obstructive sleep apnea and restless leg syndrome.

"Sleep Disorders and Fibromyalgia." Roizenblatt S, Neto NS, Tufik S. Curr Pain Headache Rep. 2011 May 20.

In clinical practice, polysomnograms ("sleep studies") are seldom ordered for patients with fibromyalgia, although sleep issues dominate the symptom complex. One reason for this is the lack of understanding how information from these studies could aid clinical decisions.

The authors conducted a chart review of one rheumatologist's community-based practice where polysomnograms were offered routinely to all women who met the American College of Rheumatology criteria for fibromyalgia. Interpretation of these standardized protocol-based polysomnograms was performed by a board-certified neurologist using standard criteria.

Restless legs were detected in polysomnograms among many women who clinically denied it (mean leg movement index 5.8).


"Sleep-disordered breathing among women with fibromyalgia syndrome." Shah MA, Feinberg S, Krishnan E. J Clin Rheumatol. 2006 Dec;12(6):277-81.

Women with FMS were more likely to have had reproductive health or sleep-related diagnoses, including premenstrual syndrome, dysmenorrhea, breast cysts, bladder cystitis, sleep apnea, restless leg syndrome, and abnormal leg movements (p < 0.0125).

"Women's health issues with fibromyalgia syndrome." Shaver JL, Wilbur J, Robinson FP, Wang E, Buntin MS. J Womens Health (Larchmt). 2006 Nov;15(9):1035-45.

Fibromyalgia is a chronic syndrome characterized by widespread pain, unrefreshed sleep, disturbed mood, and fatigue. Until such time as we have a clearer understanding of the trigger and/or pathophysiologic mechanisms producing these symptoms, pharmacologic treatment should be aimed at individual symptoms.

The main symptoms that should be addressed include pain, sleep disturbances including restless leg syndrome, mood disturbances, and fatigue.


"Pharmacologic treatment of fibromyalgia." Barkhuizen A. Curr Pain Headache Rep. 2001 Aug;5(4):351-8.

Fibromyalgia is a chronic soft tissue pain syndrome characterized by the presence of widespread musculosceletal aching, tender points at characteristic sites, fatigue and poor sleep. Associated disorders are restless leg syndrome, irritable bowel syndrome, irritable bladder syndrome, cognitive dysfunction, cold intolerance, multiple sensitivities and dizziness.

"Panalgesia and the fibromyalgia concept." Siegmeth W. Wien Med Wochenschr. 1999;149(19-20):558-60.

inflammation and disease
Winkelman et al. performed 2 separate analyses of data from large databases. An initial analysis of 2821 individuals from the Wisconsin Sleep Cohort noted cardiovascular disease to be more prevalent in individuals with daily RLS, compared with those without RLS (OR = 2.58, 95% CI 1.38-4.84)

"Prevalence and correlates of restless legs syndrome symptoms in the Wisconsin Sleep Cohort." Winkelman JW, Finn L, Young T. Sleep Med. 2006;7:545–52.

"Associations of restless legs syndrome and cardiovascular disease in the Sleep Heart Health Study." Winkelman JW, Shahar E, Sharief I, Gottlieb DJ. Neurology. 2008;70:35–42.


In a study by Ulfberg et al., 4000 men aged 18 to 64 years in central Sweden were mailed questionnaires that adhered to the 4 criteria for RLS developed by the International RLS Study Group. The prevalence of RLS was 5.8% in this sample after adjusting for eligibility, incomplete questionnaires, and nonresponder rates. RLS sufferers were more likely to report hypertension (odds ratio [OR] 1.5; 95% confidence interval [CI] 0.9-2.4) and heart problems (OR 2.5; 95% CI 1.4-4.3).

"Prevalence of restless legs syndrome among men aged 18 to 64 years: an association with somatic disease and neuropsychiatric symptoms." Ulfberg J, Nystrom B, Carter N, Edling C. Mov Disord. 2001;16:1159–63.


We evaluated the cross-sectional association between restless legs syndrome (RLS) and prevalent cardiovascular disease (CVD) in a large community-based sample of middle-aged and elderly subjects.

This is a cross-sectional observational study of 1,559 men and 1,874 women (mean age of 67.9 years) who were enrolled in the Sleep Heart Health Study, a community-based study of the cardiovascular consequences of sleep-disordered breathing.

RLS was present in 6.8% of women (n = 128) and 3.3% of men (n = 51). After adjustment for age, sex, race, body mass index, diabetes mellitus, systolic blood pressure, antihypertensive medication use, total:high-density lipoprotein cholesterol ratio, and smoking history, the ORs for CAD were 2.05 (95% CI 1.38 to 3.04) and for CVD were 2.07 (1.43 to 3.00) for subjects with RLS compared to those without RLS. The associations of RLS with CAD and CVD were stronger in those with RLS symptoms at least 16 times per month and were stronger in those with severe than in those with moderately bothersome symptoms.

Restless legs syndrome (RLS) is associated with prevalent coronary artery disease and cardiovascular disease. This association appears stronger in those with greater frequency or severity of RLS symptoms.


"Association of restless legs syndrome and cardiovascular disease in the Sleep Heart Health Study." Winkelman JW, Shahar E, Sharief I, Gottlieb DJ. Neurology. 2008 Jan 1;70(1):35-42.

Evidence is reviewed documenting an intimate relationship among restless legs syndrome (RLS) / periodic limb movements in sleep (PLMS) and hypertension and cardiovascular and cerebrovascular disease.

The results of epidemiologic studies suggest a possible relationship between self-reported RLS symptoms and daytime hypertension and are more consistent in pointing to a relationship between RLS and cardiovascular disease.


"Review of the Relationship of Restless Legs Syndrome and Periodic Limb Movements in Sleep to Hypertension, Heart Disease, and Stroke." Arthur S. Walters, MD1 and David B. Rye, MD, PhD2. Sleep. 2009 May 1; 32(5): 589–597.

inflammation and disease
The lifetime prevalence of restless legs syndrome (RLS) is about 10 % in the general population. The association of RLS with HIV infection is unknown. We aimed to investigate the prevalence of RLS in HIV positive patients and to define predictors.

33.3% of the HIV infected patients and 7% of the controls (p <0.001) fulfilled the diagnostic criteria for RLS. The mean RLS severity score was higher in HIV infected patients (19.5 +/- 7.2) than in controls (7.3 +/- 1.5; p <0.001) and correlated inversely with the CD4(+) cell count (r = -0.381; p = 0.024) and the BMI (r = -0.548; p <0.001) but not with other disease-specific factors.

In our study, HIV infected patients show a significantly higher prevalence rate for RLS than the general population. The HIV infection itself with its immunological changes and involvement of the central nervous system may predispose for a risk of RLS in HIV infected patients.


"Comorbidity of restless legs syndrome and HIV infection." Happe S, Kundmüller L, Reichelt D, Husstedt IW, Evers S. J Neurol. 2007 Oct;254(10):1401-6. Epub 2007 Oct 15.

inflammation and disease
Restless legs syndrome (RLS) is linked to gastrointestinal disorders. The prevalence of irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) in RLS patients was determined.

RLS subjects were recruited from unbiased ads that did not mention gastrointestinal symptoms. RLS diagnosis was confirmed by a neurologist and utilized the International RLS Study Group criteria. General population controls (GPC) were spouses of gastrointestinal clinic patients and were excluded for RLS. Completely healthy controls (CHC) were excluded for RLS and gastrointestinal symptoms. IBS was diagnosed by Rome II criteria. SIBO was diagnosed by the lactulose breath test (LBT).

There were 32 RLS subjects (23F/9M; 57 yo), 25 GPC (13F/12M; 58 yo) and 30 CHC (19F/11M; 44 yo). Twenty-nine had RLS unassociated with other GI diseases, one had celiac disease, and two had gastric resections. IBS was diagnosed in 28% of RLS subjects compared to 4% GPC (p=0.0317). SIBO was diagnosed in 69% of RLS subjects compared to 28% of GPC (p=0.0033) and 10% of CHC. Using a false positive rate of 10%, 59% of positive LBT results are associated with RLS.

IBS and SIBO are common in RLS. Three hypotheses developed are (a) RLS patients are selectively immunocompromised or genetically predisposed and thus more subject to SIBO; (b) SIBO leads to autoimmune changes, and subsequent auto-antibodies attack brain and/or peripheral nerves and (c) SIBO inflammation leads to increased hepcidin and CNS iron deficiency which, in turn, leads to RLS. These hypotheses bear further investigation.


"Restless legs syndrome is associated with irritable bowel syndrome and small intestinal bacterial overgrowth." Weinstock LB, Walters AS. Sleep Med. 2011 May 12.

Small intestinal bacterial overgrowth (SIBO) occurs in irritable bowel syndrome (IBS) and fibromyalgia. Since restless legs syndrome (RLS) occurs with fibromyalgia, a link between IBS, SIBO, and RLS was studied.

Ten of 13 patients exhibited > or =80% improvement from baseline in RLS symptoms. Five maintained complete resolution of RLS symptoms. Global gastrointestinal symptom improvement was great (n = 6), moderate (n = 5), or mild (n = 2).

This study suggests that SIBO associated with IBS may be a factor in some RLS patients and SIBO therapy provides long-term RLS improvement.


"Restless legs syndrome in patients with irritable bowel syndrome: response to small intestinal bacterial overgrowth therapy." Weinstock LB, Fern SE, Duntley SP. Dig Dis Sci. 2008 May;53(5):1252-6. Epub 2007 Oct 13.

inflammation and disease
RLS is a frequent and distressing comorbidity in end stage renal disease (ESRD). For idiopathic RLS (iRLS), genetic risk factors have been identified, but their role in RLS in ESRD has not been investigated yet.

"MEIS1 and BTBD9: genetic association with restless leg syndrome in end stage renal disease." Schormair B, Plag J, Kaffe M, Groß N, Czamara D, Samtleben W, Lichtner P, Ströhle A, Stefanidis I, Vainas A, Dardiotis E, Sakkas GK, Gieger C, Müller-Myhsok B, Meitinger T, Heemann U, Hadjigeorgiou GM, Oexle K, Winkelmann J. J Med Genet. 2011 May 14.

Restless legs syndrome (RLS) is a common and often misdiagnosed entity among the general population and it may be more common among dialysis patients, with an estimated prevalence of 6.6 to 21.5%.

"The pharmacological treatment for uremic restless legs syndrome: evidence-based review." de Oliveira MM, Conti CF, Valbuza JS, de Carvalho LB, do Prado GF. Mov Disord. 2010 Jul 30;25(10):1335-42.

The prevalence of sleep disorders is higher in patients with kidney failure than the general population. We studied the prevalence of sleep disorders in 88 (mean age; 41.59 +/- 16.3 years) chronic hemodialysis (HD) patients at the Urology and Nephrology Center, Mansoura University, Egypt over 4-month period. The investigated sleep disorders included insomnia, restless leg syndrome (RLS), obstructive sleep apnea syndrome (OSAS), excessive daytime sleepiness (EDS), narcolepsy and sleep walking.

"Sleep disorders in hemodialysis patients." Sabry AA, Abo-Zenah H, Wafa E, Mahmoud K, El-Dahshan K, Hassan A, Abbas TM, Saleh Ael-B, Okasha K. Saudi J Kidney Dis Transpl. 2010 Mar;21(2):300-5.

Sleep apnea (SA) is common in patients with end-stage renal disease (ESRD) and such patients are likely to suffer additional sleep disruption associated with restless legs syndrome (RLS) and periodic leg movements (PLM). Our objective was to evaluate sleep quality in ESRD patients who are newly diagnosed with SAand determine the additional contribution of PLM to sleep disruption.

The prevalence of RLS was higher in ESRD patients (60% vs 6%, p < 0.001). ESRD patients had shorter total sleep time (TST) (264 +/- 78 vs 330 +/- 46 min, p = 0.01), lower sleep efficiency (68 +/- 20 % vs 81 +/- 11 %, p = 0.03), and more stage 1 NREM sleep (23 +/- 18 vs 8 +/- 5 % TST, p = 0.002). ESRD patients had a higher frequency of PLM (31 +/- 37 hr-1 vs 8.0 +/- 16 hr-1, p = 0.02) and PLM-related arousals (15 +/- 18 hr-1 vs 1 +/- 2 hr-1, p = 0.003). Actigraphy demonstrated a higher movement and fragmentation index in ESRD patients (23 +/- 10 % sleep time vs 17 +/- 6 % sleep time, p = 0.04).


"Sleep disruption in patients with sleep apnea and end-stage renal disease." Loewen A, Siemens A, Hanly P. J Clin Sleep Med. 2009 Aug 15;5(4):324-9.

Many patients with end stage renal disease (ESRD) undergoing dialysis therapy suffer from sleep disturbances. The aim of this study was to investigate the prevalence of sleep disorders in a large population of uraemic patients recruited from 20 different dialytic centres in Triveneto.

The questionnaire revealed the presence of insomnia (69.1%), RLS (18.4%), OSAS (23.6%), EDS (11.8%), possible narcolepsy (1.4%), sleepwalking (2.1%), nightmares (13.3%) and possible RBD (2.3%). Eighty percent demonstrated SLEEP+, having at least one sleep disorder. Independent risk factors for sleep disorders were advanced age (P<0.001), excessive alcohol intake (P<0.04), cigarette smoking (P<0.006), polyneuropathy (P<0.05) and dialysis shift in the morning (P<0.001).


"Sleep disorders in patients with end-stage renal disease undergoing dialysis therapy." Merlino G, Piani A, Dolso P, Adorati M, Cancelli I, Valente M, Gigli GL. Nephrol Dial Transplant. 2006 Jan;21(1):184-90. Epub 2005 Sep 6.

Sleep disorders are common in adult dialysis patients, with a prevalence of 60%-80%.

The presence of a "sleep disturbance" was defined by positive responses in any of the four symptom domains. Overall, 18 (86%) of the children undergoing dialysis [mean age (SD) 14.2 years (1.1), gender (M/F) 11/10] endorsed sleep disturbance symptoms: sleep-disordered breathing (46%), RLS/PLMs (29%), and excessive daytime sleepiness (60%). We conclude that sleep disturbances are very common in pediatric dialysis patients, but may be underrecognized. Given the adverse neurocognitive and physiological outcomes associated with poor sleep, it is important for practitioners caring for children on dialysis to anticipate and screen for treatable sleep conditions.


"Sleep disturbances in pediatric dialysis patients." Davis ID, Baron J, O'riordan MA, Rosen CL. Pediatr Nephrol. 2005 Jan;20(1):69-75. Epub 2004 Nov 24.

Restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS) are disorders that are common and disturbing to uremic patients.

"Effect of pergolide on restless legs and leg movements in sleep in uremic patients." Pieta J, Millar T, Zacharias J, Fine A, Kryger M. Sleep. 1998 Sep 15;21(6):617-22.

A total of 49 non-dialysis-dependent children (30 with non-renal transplant CKD and 19 with post-renal transplant CKD; median age, 14 years; interquartile range, 6-18 years) were administered the pediatric sleep questionnaire; 71% (n = 35) of the patients were male; 37% (n = 18) were identified as having a sleep disorder; 40% (n = 12) were in the nontransplant CKD group and 32% (n = 6) in the transplant CKD group. The most common type of sleep disorder was RLS/PLM, affecting 27% (n = 8) in the nontransplant CKD group and 32% (n = 6) in the transplant CKD group.

"Sleep disturbances in children and adolescents with non-dialysis-dependent chronic kidney disease." Sinha R, Davis ID, Matsuda-Abedini M. Arch Pediatr Adolesc Med. 2009 Sep;163(9):850-5.

inflammation and disease
This study is the first investigation of RLS prevalence in liver dysfunction. This select population of medically complex patients who all have some degree of liver dysfunction appear to have a surprisingly high prevalence of RLS symptoms. While much of this prevalence may be the result of known secondary causes further investigation is warranted to explore the relationship between RLS and liver dysfunction.

"The high prevalence of restless legs syndrome symptoms in liver disease in an academic-based hepatology practice." Franco RA, Ashwathnarayan R, Deshpandee A, Knox J, Daniel J, Eastwood D, Franco J, Saeian K. J Clin Sleep Med. 2008 Feb 15;4(1):45-9.

Wilson's disease is an inherited disorder in which there is too much copper in the body's tissues. The excess copper damages the liver and nervous system.

Fifty-five patients with WD (22 hepatic, 28 neurological, five asymptomatic form) and 55 age- and sex-matched control subjects completed a questionnaire concerning their sleep habits, sleep co-morbidity.

One-third of the patients with WD were found to have short or borderline multiple sleep latency test (MSLT) values independent of nocturnal pathology (sleep apnoea, periodic leg movements and/or restless leg syndrome).


"Wilson's disease (Hepatolenticular degeneration)". Wilson's disease. Kaler SG. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 230.

"Sleep disorders in Wilson's disease." Nevsimalova S, Buskova J, Bruha R, Kemlink D, Sonka K, Vitek L, Marecek Z. Eur J Neurol. 2011 Jan;18(1):184-90. doi: 10.1111/j.1468-1331.2010.03106.x.


Hepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus (HCV).[1] The infection is often asymptomatic, but once established, chronic infection can progress to scarring of the liver (fibrosis), and advanced scarring (cirrhosis).

The natural course of chronic hepatitis C varies considerably from one person to another. Although almost all people infected with HCV have evidence of inflammation on liver biopsy, the rate of progression of liver scarring (fibrosis) shows significant variability among individuals.

A series of nine patients with neurologic complications of hepatitis C virus infection is reported. Seven patients presented a combination of chronic sensory polyneuropathy, multineuropathy, and encephalopathy related to cryoglobulinemia. The noncryoglobulinemic symptoms consisted of an anterior optic neuropathy and a restless legs syndrome with small-fiber neuropathy. Corticosteroids and cyclophosphamide were useful in controlling vasculitic episodes. Interferon-alpha caused remission in half of the treated patients.


"Hepatitis C." Wikipedia en.wikipedia.org/wiki/Hepatitis_C

"Neurologic complications associated with hepatitis C virus infection." Tembl JI, Ferrer JM, Sevilla MT, Lago A, Mayordomo F, Vilchez JJ. Neurology. 1999 Sep 11;53(4):861-4.


inflammation and disease
Our objective is to determine the prevalence of restless legs syndrome (RLS) in women with systemic lupus erthythematosus (SLE), and to compare this to a rheumatic disease sample without SLE.

Unselected consecutive female patients were SLE were recruited from a lupus clinic. A RLS questionnaire based on 4 criteria, validated by the International Restless Legs Syndrome Study Group, was administered during a face-to-face interview. Smoking history and height and weight data were collected. Similar methods were used to determine RLS prevalence in a comparator group of women with rheumatic diseases other than SLE. Controls were frequency-matched by age group (in 5-year age bands) to SLE subjects. Controls were otherwise unselected.

We recruited 33 women with SLE and 32 controls. Twelve of 33 female SLE subjects scored positively for RLS (37.5%; 95% CI 22.9, 54.7) compared to 4 of 32 controls (12.5%; 95% CI 5.0, 28.1). Multivariate logistic regression showed that adjusted for age, obesity, and smoking, women with SLE were more likely to have RLS than the female controls (adjusted odds ratio 6.61, 95% CI 1.52, 28.77). In our multivariate analyses of all rheumatic patients, including SLE, the adjusted OR for obesity and RLS was 5.14 (95% CI 1.07, 24.6).

These novel data indicate that RLS is more prevalent in women with SLE than in controls. Although obesity was a significant risk factor for RLS in our sample, the predictive covariates examined were limited.


"Systemic lupus and risk of restless legs syndrome." Hassan N, Pineau CA, Clarke AE, Vinet E, Ng R, Bernatsky S. J Rheumatol. 2011 May;38(5):874-6. Epub 2011 Feb 15.

inflammation and disease
A study was undertaken in and from an eastern Pennsylvania private psychiatric office to ascertain the likelihood of a Lyme/RLS connection in that area, highly endemic for infected deer ticks.

Of the 66 chronically Lyme-infected psychiatric office outpatients, 20% described typical symptoms of Restless Legs Syndrome. They acknowledged RLS symptoms as causing excruciating distress to them.


"Restless Leg Syndrome As A Marker For Unsuspected Chronic Lyme Disease." Virginia T. Sherr, MD Wellsphere www.wellsphere.com/lyme-disease-article/restless-leg-syndrome-as-a-marker-for-unsuspected-chronic-lyme-disease/348430

inflammation and disease
Sleep disorders have been described in migraine patients. Among sleep disorders RLS has been reported in up to one-third of migraineurs. Adverse effects of anti migraine therapy by dopamine antagonists can not fully explain this association. Therefore we present the hypothesis that RLS and migraine may have a joint origin. The hypothesis is supported by: (1) the same genetic origin for migraine without aura and RLS in single Italian family on chromosome 14q21; this gene codes survival motor neuron-interacting protein 1 (SIP1) which can play role in both diseases. (2) Correlation of both RLS and migraine with fibromyalgia. (3) Alteration of cortical excitability in both migraine and RLS.

"Possible joint origin of restless leg syndrome (RLS) and migraine." Sabayan B, Bagheri M, Borhani Haghighi A. Med Hypotheses. 2007;69(1):64-6. Epub 2007 Jan 26.

The purpose of our study was to determine the patterns of isolated lesser saphenous vein (LSV) system incompetence and correlate the distribution and extent of such reflux with symptoms and signs of chronic venous disease (CVD).

There were 174 patients (87%) with unilateral and 26 with bilateral disease, and 41% of the limbs belonged in CVD class 2, 26% in class 3, 12% in class 4, 3.5% in class 5, and 3% in class 6. Classes 0 and 1 were present in 14.5% of the limbs. Symptoms were present in 139 limbs (61.5%). Some degree of ache or burning sensation was the most frequent symptom (41%), followed by itching (32%), heaviness (29%), cramps (24%), and restless limbs (18%).


"The impact of isolated lesser saphenous vein system incompetence on clinical signs and symptoms of chronic venous disease." Labropoulos N, Giannoukas AD, Delis K, Kang SS, Mansour MA, Buckman J, Katsamouris A, Nicolaides AN, Littooy FN, Baker WH. J Vasc Surg. 2000 Nov;32(5):954-60.

inflammation and disease
In this study, we aimed to investigate whether or not the increased RLS frequency seen in MS could be associated with depression and fatigue.
The study involved 98 patients with definite MS and 129 healthy volunteers. The Beck Depression Inventory and Fatigue Severity Scale were used to assess all participants. The patients and the healthy volunteers were examined for RLS according to the criteria of the International Restless Legs Syndrome Study Group.
When the factors related to RLS in MS were evaluated, there were significant relationships found among age, type of MS, pyramidal symptoms, intestinal and bladder symptoms, number of lesions in MR, depression, and fatigue. Risk factors for RLS were also seen more frequently in the MS group than in the healthy volunteers.
RLS was seen 2.55 times more frequently in patients with MS than in the control group. This was due to the existence of numerous factors rather than a single factor - including depression and fatigue.


"Restless legs syndrome in multiple sclerosis." Aydar G, Kurt S, Karaer Unaldi H, Erkorkmaz U. Eur Neurol. 2011;65(5):302-6. Epub 2011 May 13.

RLS is significantly associated with MS, especially in patients with severe pyramidal and sensory disability. These results strengthen the idea that the inflammatory damage correlated with MS may induce a secondary form of RLS. As it does in idiopathic cases, RLS has a significant impact on sleep quality in patients with MS; therefore, it should be always searched for, particularly in the presence of insomnia unresponsive to treatment with common hypnotic drugs.

"Multicenter case-control study on restless legs syndrome in multiple sclerosis: the REMS study." Manconi M, Ferini-Strambi L, Filippi M, Bonanni E, Iudice A, Murri L, Gigli GL, Fratticci L, Merlino G, Terzano G, Granella F, Parrino L, Silvestri R, Aricò I, Dattola V, Russo G, Luongo C, Cicolin A, Tribolo A, Cavalla P, Savarese M, Trojano M, Ottaviano S, Cirignotta F, Simioni V, Salvi F, Mondino F, Perla F, Chinaglia G, Zuliani C, Cesnik E, Granieri E, Placidi F, Palmieri MG, Manni R, Terzaghi M, Bergamaschi R, Rocchi R, Ulivelli M, Bartalini S, Ferri R, Lo Fermo S, Ubiali E, Viscardi M, Rottoli M, Nobili L, Protti A, Ferrillo F, Allena M, Mancardi G, Guarnieri B and Londrillo F. Sleep. 2008 Jul;31(7):944-52.

We have tested the hypothesis that restless leg syndrome (RLS) is related to quality of sleep, fatigue and clinical disability in multiple sclerosis (MS). The diagnosis of RLS used the four minimum criteria defined by the International Restless Legs Syndrome Study Group. Fatigue was assessed by the Fatigue Severity Scale (FSS >27), quality of sleep by the Pittsburgh Sleep Quality Index (PSQI >6), excessive daytime sleepiness by the Epworth Sleepiness Scale (ESS >10) and clinical disability by the Expanded Disability Status Scale (EDSS). Forty-four patients (32 women) aged 14 to 64 years (43 +/- 14) with disease from 0.4 to 23 years (6.7 +/- 5.9) were evaluated. Thirty-five were classified as relapsing-remitting, 5 as primary progressive and 4 as secondary progressive. EDSS varied from 0 to 8.0 (3.6 +/- 2.0). RLS was detected in 12 cases (27%). Patients with RLS presented greater disability (P = 0.01), poorer sleep (P = 0.02) and greater levels of fatigue (P = 0.03). Impaired sleep was present in 23 (52%) and excessive daytime sleepiness in 3 cases (6.8%). Fatigue was present in 32 subjects (73%) and was associated with clinical disability (P = 0.000) and sleep quality (P = 0.002). Age, gender, disease duration, MS pattern, excessive daytime sleepiness and the presence of upper motor neuron signs were not associated with the presence of RLS. Fatigue was best explained by clinical disability and poor sleep quality. Awareness of RLS among health care professionals may contribute to improvement in MS management.

"Restless leg syndrome, sleep quality and fatigue in multiple sclerosis patients." Moreira NC, Damasceno RS, Medeiros CA, Bruin PF, Teixeira CA, Horta WG, Bruin VM. Braz J Med Biol Res. 2008 Oct;41(10):932-7.

Despite the fact that multiple sclerosis (MS) patients often include leg restlessness as a sensory symptom, MS is not mentioned amongst symptomatic restless legs syndrome (RLS) forms. RLS is a very common finding in MS patients and should be considered amongst the symptomatic RLS forms. RLS is also associated with higher disability.

"High prevalence of restless legs syndrome in multiple sclerosis." Manconi M, Fabbrini M, Bonanni E, Filippi M, Rocca M, Murri L, Ferini-Strambi L. Eur J Neurol. 2007 May;14(5):534-9.

Progressive systemic sclerosis (SSc) is a connective tissue disease characterized by endothelial lesions and fibrosis of the skin and other organs. Patients' quality of life and life expectancy are determined by the intensity of pulmonary, esophageal, cardiac, and renal involvement.

Patients with SSc have significant disturbance of their sleep. Esophageal dyskinesia and dyspnea, which are common complications of SSc, were commonly associated with indices of sleep disruption. RLS but not sleep apnea appears to have an increased prevalence in SSc.


"Sleep disruption in systemic sclerosis (scleroderma) patients: clinical and polysomnographic findings." Prado GF, Allen RP, Trevisani VM, Toscano VG, Earley CJ. Sleep Med. 2002 Jul;3(4):341-5.

inflammation and disease
Our study investigated the occurrence of restless legs syndrome (RLS) in narcolepsy with cataplexy (NC) using a case-control study assessing the frequency of comorbidity of RLS and NC in three European sleep disorder centers.

NC patients and controls underwent a face-to-face interview investigating demographics, medical and drug history, sleep habits, and sleep disorders, in particular RLS based on the 4 international criteria and on a frequency > or =2 times/week, with a detailed description of RLS symptoms when present. RLS was significantly more prevalent among NC patients (14.7%) than in controls (3.0%). The age at onset of RLS in NC patients fits with the age at onset in idiopathic RLS, and RLS appeared more than 10 years after NC onset. Unlike idiopathic RLS, RLS in NC subjects was not more prevalent in women and was less familial (15.4% of cases). Lastly, NC patients with RLS showed a moderate disease severity and an almost daily occurrence of symptoms, which were also diurnal in 35% of cases.

This study highlights the association between RLS and NC. The nature of this association is still investigational, but it does indicate that RLS must be addressed in the evaluation and management of nocturnal sleep impairment in NC patients.


"Restless legs syndrome is frequent in narcolepsy with cataplexy patients." Plazzi G, Ferri R, Antelmi E, Bayard S, Franceschini C, Cosentino FI, Abril B, Spruyt K, Provini F, Montagna P, Dauvilliers Y. Sleep. 2010 May;33(5):689-94.

inflammation and disease
The aim of this study was to assess the prevalence of RLS in a cohort of patients with diabetic neuropathy and to analyze the features of the associated neuropathy.

Our data show that RLS is a relevant feature of diabetic neuropathy, as a frequent and potentially treatable manifestation of small fiber involvement in the course of DM and IGT/IFG.


"Restless legs syndrome in diabetic neuropathy: a frequent manifestation of small fiber neuropathy." Gemignani F, Brindani F, Vitetta F, Marbini A, Calzetti S. J Peripher Nerv Syst. 2007 Mar;12(1):50-3.

RLS is frequent in painful polyneuropathy and is significantly associated with decreased small fiber input, thus nociceptive deafferentation may represent a factor interacting with RLS "generators," possibly at spinal level. We suggest that overactivity of the spinal structures implicated in RLS may be triggered by nociceptive deafferentation in a subgroup of patients with painful polyneuropathy.


"Restless legs syndrome and painful neuropathy-retrospective study. A role for nociceptive deafferentation?" Gemignani F, Brindani F, Vitetta F, Marbini A. Pain Med. 2009 Nov;10(8):1481-6.

The treatment of RLS demands a clinical evaluation to rule out and cure causes of secondary RLS, including iron supplementation when deficient, and to eliminate the triggering factors. The presence of neuropathy should be especially investigated in nonhereditary, late-onset RLS, in view of a possible treatment of the underlying disease.


"Restless legs syndrome: differential diagnosis and management with pramipexole." Brindani F, Vitetta F, Gemignani F. Clin Interv Aging. 2009;4:305-13. Epub 2009 Jun 29.

Restless legs syndrome (RLS) has been frequently reported in association with peripheral neuropathy, and it is especially frequent in some forms of polyneuropathy with preferential involvement of small sensory fibers. Here, we describe a patient with multifocal motor neuropathy, who developed RLS during the course of the disease. Our findings support the notion that RLS may develop in the context of immune-mediated neuropathies and it should be specifically investigated even in those patients with preferentially or exclusive motor involvement.


"Restless legs syndrome in a patient with multifocal motor neuropathy." Lo Coco D, Cannizzaro E, Lopez G. Neurol Sci. 2009 Oct;30(5):401-3. Epub 2009 Jul 2.

RLS is idiopathic, with family history in 40-60% of the cases, or symptomatic associated conditions such as iron deficiency, uremia, pregnancy, Parkinson's disease, neuropathy or myelopathy.


"Symptomatic causes of restless legs syndrome." Carrillo F, Mir P. Neurologia. 2009 Dec;24(10):841-4.

In a case-control design, 245 patients with peripheral neuropathy and 245 age- and sex-matched controls were screened for RLS using a standardized phone questionnaire based on international RLS diagnostic criteria.

When classified by etiology, RLS was found in 14/72 (19.4%) patients with hereditary neuropathy, a prevalence higher than found in controls (p = 0.016) and acquired neuropathy (9.2%, p = 0.033). Among patients with neuropathy, those with RLS more commonly had a family history of RLS (37% vs 15%, p = 0.007) and were younger (49.9 vs 61.4, p = 0.0003).

Restless legs syndrome is more prevalent among patients with hereditary neuropathy, but not in those with acquired neuropathies.


"Is there a higher risk of restless legs syndrome in peripheral neuropathy?" Erin Hattan, MD, Colin Chalk, MD, CM and Ronald B. Postuma, MD, MSc. Neurology March 17, 2009 vol. 72 no. 11 955-960

One hundred and thirty-one patients on long-term hemodialysis were examined for the presence of clinical symptoms and signs, and for the effects of dialytic age, age and sex on uremic neuropathy.

Clinical grading of uremic neuropathy was based on Nielsen's criteria. The most common symptoms were restless legs syndrome (47%) and cramps (51%).


"Clinical course of uremic neuropathy in long-term hemodialysis." Jurcic D, Bilic A, Schwarz D, Orsanic D, Gabric M, Spoljaric L, Mihanovic M. Coll Antropol. 2008 Sep;32(3):771-5.

The most common inherited neuropathies are a group of disorders collectively referred to as Charcot-Marie-Tooth disease. These neuropathies result from flaws in genes responsible for manufacturing neurons or the myelin sheath. Hallmarks of typical Charcot-Marie-Tooth disease include extreme weakening and wasting of muscles in the lower legs and feet, gait abnormalities, loss of tendon reflexes, and numbness in the lower limbs.

Charcot-Marie-Tooth disease can be associated with several disorders that may be encountered by the pulmonary physician, including restrictive pulmonary impairment, sleep apnea, restless legs, and vocal cord dysfunction.

Restless legs and periodic limb movement during sleep are found in a large proportion of patients with CMT2, a type of CMT associated with prominent axonal atrophy.


"Disorders of pulmonary function, sleep, and the upper airway in Charcot-Marie-Tooth disease." Aboussouan LS, Lewis RA, Shy ME. Lung. 2007 Jan-Feb;185(1):1-7. Epub 2007 Feb 9.

"Peripheral Neuropathy Fact Sheet." National Institute of Neurological Disorders and Stroke (February 18, 2011) www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheralneuropathy.htm

In a series of 12 patients with essential mixed cryoglobulinaemia (EMC) and peripheral neuropathy as main feature of the disease, restless legs syndrome (RLS) was a major manifestation in four women, aged 55-65 years.

The occurrence of RLS, especially in middle-aged women, should prompt investigations for peripheral neuropathy focusing on cryoglobulinaemic neuropathy.


"Cryoglobulinaemic neuropathy manifesting with restless legs syndrome." Gemignani F, Marbini A, Di Giovanni G, Salih S, Margarito FP, Pavesi G, Terzano MG. J Neurol Sci. 1997 Nov 25;152(2):218-23.
Restless legs syndrome (RLS), diagnosed according to the International RLS Study Group criteria, was investigated in 97 consecutive patients with polyneuropathy and found in 29 patients. RLS patients were more often women (22 of 29 vs. 33 of 68; P = 0.015), mainly with sensory neuropathy of small fiber type (15 of 29 vs. 16 of 68; P = 0.009). Changes of sensory action potentials were significantly less severe in RLS patients. In the RLS group, acquired neuropathies, and in particular dysimmune neuropathies, were significantly more frequent (27/29 vs. 46/68; P = 0.009). Thus, RLS is frequent in acquired polyneuropathy of sensory type and mild entity, mainly in women.

"Restless legs syndrome and polyneuropathy." Gemignani F, Brindani F, Negrotti A, Vitetta F, Alfieri S, Marbini A. Mov Disord. 2006 Aug;21(8):1254-7.

inflammation and disease
Obesity and restless legs syndrome (RLS) are both associated with hypofunction of dopamine in the CNS. We therefore examined whether individuals who are obese have an increased risk of RLS in two ongoing US cohorts, the Nurses' Health Study II and the Health Professional Follow-up Study.

We included 65,554 women and 23,119 men free of diabetes, arthritis, and pregnancy in the current analyses. Information on RLS was assessed using a set of standardized questions.

Our study shows both overall and abdominal adiposity are associated with increased likelihoods of having restless legs syndrome (RLS). Further prospective studies are warranted to clarify causative association between obesity and risk of developing RLS.


"Obesity and restless legs syndrome in men and women." Gao X, Schwarzschild MA, Wang H, Ascherio A. Neurology. 2009 Apr 7;72(14):1255-61.

A new study shows both obesity and a large belly appear to increase the risk of developing restless legs syndrome.

The research found men and women with a body mass index (BMI) score over 30 were nearly one-and-a-half times more likely to have RLS than people who were not obese.

In addition, people who were in the top 20 percent of the group for highest waist circumference were more than one-and-a-half times more likely to have RLS than the bottom 20 percent of the group with the lowest belly size. The results were the same regardless of age, smoking, use of antidepressants or anxiety.


"Big Belly and Obesity Linked to Increased Risk of Restless Legs Syndrome." American Academy of Neurology, Apr. 6 2009. www.aan.com

Pneumologists frequently see obese and diabetic patients because of the high prevalence of these pathologies associated with sleep apneas. Nevertheless, the search for a sleep apnea syndrome is sometimes negative and the pneumologist is faced with unexplained complaints of sleepiness and sleep disorders. Pneumologists have to be familiar with and explore other nonrespiratory disorders in order to improve patient care. Inflammatory mechanisms have been suspected in several recent studies on daytime sleepiness. Sleep duration, obesity and diabetes are supposed to be linked because of hormonal modifications induced by sleep deprivation. Moreover, a relationship between diabetes and restless legs syndrome is not excluded.


"Nonrespiratory sleep disorders in obese and diabetic patients." Bayon V, Leger D, Laaban JP. Rev Pneumol Clin. 2009 Apr;65(2):67-74. Epub 2009 Mar 28.

inflammation and disease
Our objective was to investigate the clinical feature of Parkinson's disease (PD) with restless leg syndrome (RLS) and the pathogenesis of RLS. We conducted a cross-sectional and control study. The case group concluded 31 PD with RLS patients, meanwhile 39 PD patients were selected as the control group. Clinical history, clinical manifestations, complications and laboratory examinations were compared respectively between the two groups.

All the RLS symptoms did not appear in RLS patients until the PD symptoms came out. Significant differences were found in complications such as swallow disturbance, constipation and illusion, when we compared the two PD groups (P < 0.05). Compared with the PD or healthy group, the level of serum ferritin and the H-reflex latency of tibial nerve were significantly decreased in PD with RLS group (P < 0.05).

We conclude that secondary RLS is a complication of PD. Deficiency of iron and decreased inhibition function of spinal cord may lead to the occurrence of RLS in PD patients. When their motor symptoms are serious and complications are more common, PD patients are more possible to have RLS symptoms.


"The clinical research of restless leg syndrome and Parkinson's disease]." Zhao LQ, Wang LN, Hu FY. Zhonghua Nei Ke Za Zhi. 2010 Nov;49(11):947-50.

Corticobasal ganglionic degeneration (which we will call CBD) is a rare progressive neurological disorder characterized by a combination of Parkinsonism and cortical dysfunction.

All five patients with corticobasal degeneration (CBD) had insomnia, four displayed periodic limb movements during sleep (PLMS) and/or restless leg syndrome (RLS), and two had sleep respiratory disorders. None had REM sleep behaviour disorders or excessive daytime sleepiness.


"Corticobasal ganglionic degeneration (CBD)," Timothy C. Hain, MD dizziness-and-balance.com (2001)

"Sleep and vigilance in corticobasal degeneration: a descriptive study." Roche S, Jacquesson JM, Destée A, Defebvre L, Derambure P, Monaca C. Neurophysiol Clin. 2007 Aug-Sep;37(4):261-4. Epub 2007 Jun 26.


Sleep disturbances are frequent in Parkinson disease. These disorders can be broadly categorized into those that involve nocturnal sleep and excessive daytime sleepiness. The disorders that are often observed during the night in PD include sleep fragmentation that may be due to recurrent PD symptoms, sleep apnea, Restless Leg Syndrome/ periodic limb movements and REM sleep behavior disorder.

"Sleep disturbances and excessive daytime sleepiness in Parkinson disease: an overview." Comella CL. J Neural Transm Suppl. 2006;(70):349-55.

A large number of patients with Parkinson's disease (PD) experience nocturnal problems that impair their sleep quality. Among them, motor disorders such as tremor, rigidity, akinesia, akathisia, periodic leg movements, painful dystonia, dyskinesias, restless legs syndrome, and rapid eye movement sleep behavior disorder are common.

"Nocturnal problems occurring in Parkinson's disease." Grandas F, Iranzo A. Neurology. 2004 Oct 26;63(8 Suppl 3):S8-11.

Nocturnal disturbances are common in Parkinson's disease (PD) patients, with almost 70% of these patients reporting nocturnal disturbances. Nocturnal disturbances can be categorized in four groups: 1) PD-related motor symptoms, including nocturnal akinesia, early-morning dystonia, painful cramps, tremor, and difficulty turning in bed; 2) treatment-related nocturnal disturbances; 3) psychiatric symptoms, including hallucinations, vivid dreams, depression, dementia, insomnia, psychosis, and panic attacks; 4) other sleep disorders, including insomnia, REM behavioral disorder (RBD), restless legs syndrome (RLS), periodic leg movements (PLMS), and excessive daytime sleepiness (EDS).

"Treatment of nocturnal disturbances and excessive daytime sleepiness in Parkinson's disease." Barone P, Amboni M, Vitale C, Bonavita V. Neurology. 2004 Oct 26;63(8 Suppl 3):S35-8.

We examined whether men with restless legs syndrome (RLS) have a higher prevalence of Parkinson's disease (PD) among 23,119 US participants of the Health Professional Follow-up Study who were free of diabetes and arthritis.

Our study shows that men with RLS are more likely to have concurrent PD. Prospective studies are warranted to clarify the temporal relationship between RLS and PD.


"Restless legs syndrome and Parkinson's disease in men." Gao X, Schwarzschild MA, O'Reilly EJ, Wang H, Ascherio A. Mov Disord. 2010 Nov 15;25(15):2654-7.

inflammation and disease
This study evaluated the prevalence of sleep-related and sleep-disordered-breathing (SDB)-related complaints in a group of postpolio patients compared with healthy controls.

A questionnaire, consisting of the validated Sleep Wake Experience List (SWEL), and a list of questions pertaining to sleep-disordered breathing (SDB), was mailed to a group of 43 postpolio patients.

The patient group consisted of 43 former polio patients who had been evaluated at a neuromuscular disease clinic in a tertiary referral center for new complaints of progressive muscle weakness. The patients were requested to select two healthy controls from their neighborhood who also filled out a questionnaire.

In the group of postpolio patients the frequency of tiredness on waking up and during the day, headache on waking up, daytime sleepiness, and restless legs was significantly higher compared with the control group. Complaints specifically related to SDB, such as apneas and snoring, were not mentioned significantly more often by the postpolio patients.

Up to half of postpolio patients report complaints of disordered sleep, which is likely to influence daytime functioning. Further studies, including sleep studies into SDB and restless legs, are necessary to elucidate the causes for these complaints.


"Sleep complaints in postpolio syndrome." van Kralingen KW, Ivanyi B, van Keimpema AR, Venmans BJ, de Visser M, Postmus PE. Arch Phys Med Rehabil. 1996 Jun;77(6):609-11.


Post-polio syndrome (PPS) is a condition that affects polio survivors years after recovery from an initial acute attack of the poliomyelitis virus. Most often, polio survivors start to experience gradual new weakening in muscles that were previously affected by the polio infection and also in muscles that seemingly were unaffected by the virus.

Proper lifestyle changes, especially with regard to eating style and body weight control, the use of assistive devices, and taking certain anti-inflammatory medications may help some of the symptoms of PPS.

Determining if there is an immunological link in PPS is also an area of intense interest. Researchers who discovered inflammation around motor neurons or muscles are trying to find out if this is due to an immunological response.

Restless legs syndrome (RLS) has been described in association with a number of conditions including iron deficiency, neuropathy and Parkinson's disease. Here we report a patient who developed RLS concurrent with the development of classic post-polio syndrome (PPS), 40 years after recovery from an episode of paralytic poliomyelitis. PPS is still frequently encountered in neurological practice, and clinicians should be aware of the possibility of associated RLS.


"Restless legs may be associated with the post-polio syndrome." De Grandis E, Mir P, Edwards MJ, Bhatia KP. Parkinsonism Relat Disord. 2009 Jan;15(1):74-5. Epub 2008 Mar 28.

"Post-Polio Syndrome Fact Sheet." National Institute of Neurological Disorders and Stroke (June 6, 2011) www.ninds.nih.gov/disorders/post_polio/detail_post_polio.htm


Few studies have described the occurrence of restless legs syndrome in post-polio syndrome.

We studied 10 consecutive patients with post-polio syndrome and symptoms of restless legs syndrome. We look at demographic, clinical and laboratorial data.

A remarkable finding was the concomitant onset of symptoms of both diseases, suggesting a possible underlying mechanism. Severity of restless legs symptoms was moderate to very severe.

Epidemiological studies with larger samples are needed to better establish the relationship and the incidence of restless legs syndrome in post-polio syndrome.


"Restless legs syndrome in post-polio syndrome: A series of 10 patients with demographic, clinical and laboratorial findings." Marin LF, Carvalho LB, Prado LB, Quadros AA, Oliveira AS, Prado GF. Parkinsonism Relat Disord. 2011 Jun 1.

inflammation and disease
The overall prevalence of RLS was 10.6%, increasing with age, and women were twice as often affected as men. While nulliparous women had prevalences similar to those among men up to age 64 years, the risk of RLS increased gradually for women with 1 child (odds ratio, 1.98; 95% confidence interval, 1.25-3.13), 2 children (odds ratio, 3.04; 95% confidence interval, 2.11-4.40), and 3 or more children (odds ratio, 3.57; 95% confidence interval, 2.30-5.55).

"Sex and the risk of restless legs syndrome in the general population." Berger K, Luedemann J, Trenkwalder C, John U, Kessler C. Arch Intern Med. 2004 Jan 26;164(2):196-202.

Restless legs syndrome (RLS) is common in the third trimester of pregnancy. In this case-control study, 22.5% of 211 women had RLS. The RLS cases had a history of growing pains (GP) more frequently than controls (P = 0.042). A family history of GP (P = 0.025) and RLS (P = 0.018) was more frequent among cases than controls. RLS in pregnancy is predicted by family history of RLS and GP, and by childhood history of GP.

"A common sleep disorder in pregnancy: Restless legs syndrome and its predictors." Balendran J, Champion D, Jaaniste T, Welsh A. Aust N Z J Obstet Gynaecol. 2011 Jun;51(3):262-4. doi: 10.1111/j.1479-828X.2011.01294.x. Epub 2011 Mar 16.

The aim of this study was to assess the prevalence of restless legs syndrome in pregnancy. We distributed a questionnaire to 541 consecutive post-partum patients and received answers from 251 (46%) women.

Of the participants 34% reported restless legs syndrome in pregnancy. In 97% of the women where restless legs syndrome had started during the pregnancy, the symptoms disappeared within two to three days after delivery.


"Restless legs syndrome in pregnancy is a frequent disorder with a good prognosis." Uglane MT, Westad S, Backe B. Acta Obstet Gynecol Scand. 2011 Apr 19. doi: 10.1111/j.1600-0412.2011.01157.x.

The questionnaire was distributed by the medical staff in different outpatient waiting rooms (obstetrics and gynecology department of the university hospital, obstetrics and gynecology department of a private clinic, private midwives, private obstetrician-gynecologists, radiological centers before fetal ultrasound examination and general practitioners) in a French town and its surrounding area (200,000 inhabitants).

1,022 pregnant women living in a French town were included. 24% of women were affected by RLS during their pregnancy. The disease was strongly related to the third trimester of pregnancy and had a significant impact on sleep leading to severe nocturnal and diurnal consequences with a high consumption of sleep medication.


"Restless legs syndrome and pregnancy: a questionnaire study in the Poitiers District, France." Neau JP, Porcheron A, Mathis S, Julian A, Meurice JC, Paquereau J, Godeneche G, Ciron J, Bouche G. Eur Neurol. 2010;64(5):268-74. Epub 2010 Oct 27.

Restless legs syndrome (RLS) is more common in pregnant women. The objective of our study was to determine frequency of RLS in pregnant women and predictors of RLS in pregnancy in Pakistan. All pregnant women admitted at The Aga Khan University Hospital for delivery from June to July 2005 were enrolled. Eighty-one of 271 (30%) interviewed women fulfilled the diagnostic criteria of RLS.

"Predictors of restless legs syndrome in pregnancy: a hospital based cross sectional survey from Pakistan." Sikandar R, Khealani BA, Wasay M. Sleep Med. 2009 Jun;10(6):676-8. Epub 2008 Dec 24.

Our study was designed to evaluate the associated risk of RLS with pregnancy in relation to the family history and the age of symptom onset of RLS. Data from a prior RLS family history study in which 1019 subjects (527 males, 492 females) were interviewed, provided a diagnosis and characterization of RLS and determination of pregnancy status on which the current study analysis was undertaken.

In the family members of RLS probands, the prevalence of RLS was significantly higher for parous women than for nulliparous women (49.5% vs. 33.7%, OR=1.92, 95% CI=1.16-3.19) or for men (49.5% vs. 30.0%, OR 2.29, 1.69-3.10), but no different for nulliparous women compared to men (33.7% vs. 30.0%, OR 1.19, 0.72-1.96). When only those whose RLS started at or after age 30 were considered, similar differences occurred. These differences were not observed among family members of control probands.

These data indicate pregnancy has a major impact on the risk of developing RLS for those with a family history of RLS. This pregnancy effect appears to account for most of the gender differences often reported in overall RLS prevalence data.


"Pregnancy accounts for most of the gender difference in prevalence of familial RLS." Pantaleo NP, Hening WA, Allen RP, Earley CJ. Sleep Med. 2010 Mar;11(3):310-3. Epub 2009 Jul 9.

inflammation and disease
Patients with pulmonary hypertension (PH) have an increased prevalence of risk factors for restless legs syndrome (RLS). In our study, patients with PH had a very high prevalence of RLS and most had moderate or severe symptoms. RLS was more common in more active patients and those who were hypothyroid or on opioids for relief of leg pain. Patients with PH should be screened for RLS because good treatment options are available.

"Prevalence and characteristics of restless legs syndrome in patients with pulmonary hypertension." Minai OA, Malik N, Foldvary N, Bair N, Golish JA. J Heart Lung Transplant. 2008 Mar;27(3):335-40.

inflammation and disease
Progressive systemic sclerosis (SSc) is a connective tissue disease characterized by endothelial lesions and fibrosis of the skin and other organs. Conditions seen with SSc, such as pulmonary fibrosis and gastro-esophageal reflux, have the potential to affect sleep.

An all-night polysomnogram and a clinical interview blinded to sleep status were obtained for 27 consecutive SSc patients.

Patients with SSc had a reduced sleep efficiency (SE) (mean+/-SD: 82+/-12.3%) and rapid eye movement sleep (13.1+/-5.6%) and increased arousal index (26.1+/-13.0) and slow wave sleep (25.7+/-9.7%). The periodic leg movement index (PLMI) exceeded 5/h in 13 patients (48%) and 25/h in seven patients. Six patients had restless legs syndrome (RLS). Significant disordered breathing was absent. The RLS patients showed a greater arousal index than all other patients. PLMI was correlated with SE for RLS but not for non-RLS patients. Esophageal dyskinesia, dyspnea, and RLS were significantly associated with poor sleep.

Patients with SSc have significant disturbance of their sleep. Esophageal dyskinesia and dyspnea, which are common complications of SSc, were commonly associated with indices of sleep disruption. RLS but not sleep apnea appears to have an increased prevalence in SSc.


"Sleep disruption in systemic sclerosis (scleroderma) patients: clinical and polysomnographic findings." Prado GF, Allen RP, Trevisani VM, Toscano VG, Earley CJ. Sleep Med. 2002 Jul;3(4):341-5.

inflammation and disease
Restless legs syndrome (RLS) is linked to gastrointestinal disorders. The prevalence of irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) in RLS patients was determined.

RLS subjects were recruited from unbiased ads that did not mention gastrointestinal symptoms. RLS diagnosis was confirmed by a neurologist and utilized the International RLS Study Group criteria. General population controls (GPC) were spouses of gastrointestinal clinic patients and were excluded for RLS. Completely healthy controls (CHC) were excluded for RLS and gastrointestinal symptoms. IBS was diagnosed by Rome II criteria. SIBO was diagnosed by the lactulose breath test (LBT).

There were 32 RLS subjects (23F/9M; 57 yo), 25 GPC (13F/12M; 58 yo) and 30 CHC (19F/11M; 44 yo). Twenty-nine had RLS unassociated with other GI diseases, one had celiac disease, and two had gastric resections. IBS was diagnosed in 28% of RLS subjects compared to 4% GPC (p=0.0317). SIBO was diagnosed in 69% of RLS subjects compared to 28% of GPC (p=0.0033) and 10% of CHC. Using a false positive rate of 10%, 59% of positive LBT results are associated with RLS.

IBS and SIBO are common in RLS. Three hypotheses developed are (a) RLS patients are selectively immunocompromised or genetically predisposed and thus more subject to SIBO; (b) SIBO leads to autoimmune changes, and subsequent auto-antibodies attack brain and/or peripheral nerves and (c) SIBO inflammation leads to increased hepcidin and CNS iron deficiency which, in turn, leads to RLS. These hypotheses bear further investigation.


"Restless legs syndrome is associated with irritable bowel syndrome and small intestinal bacterial overgrowth." Weinstock LB, Walters AS. Sleep Med. 2011 May 12.

inflammation and disease
A standardized sleep questionnaire was used to investigate the sleeping habits of outpatients with primary Sjögren's syndrome (pSS) (n = 40) and RA (n = 42). Sleep deficit (difference between need of sleep and actual sleeping time) was significantly higher in patients with pSS when compared with healthy matched controls (P < 0.0001), and with patients suffering from RA (P < 0.001).

When trying to fall asleep, patients with pSS were significantly more often disturbed by muscular tension (45%) and restless legs (24%), than patients with RA (12%, P < 0.01 and 2%, P < 0.01), and they were also significantly more troubled by nocturnal pain than patients with RA (P < 0.01).


"Sleep disturbances in patients with primary Sjögren's syndrome." Gudbjörnsson B, Broman JE, Hetta J, Hallgren R. Br J Rheumatol. 1993 Dec;32(12):1072-6.

Our objective is to study the prevalence of fatigue and daytime sleepiness in primary SS (pSS) and analyse predicting sleep disturbing factors and other potential determinants of fatigue and sleepiness.

Sleepiness is a minor problem. Patients had significantly more often anxiety, nocturia and woke up more frequently during the night than controls. RLS, depression and sicca symptoms contributed to fatigue in the univariate regression analysis only.


"Sleepiness or fatigue? Can we detect treatable causes of tiredness in primary Sjögren's syndrome?" Theander L, Strömbeck B, Mandl T, Theander E. Rheumatology (Oxford). 2010 Jun;49(6):1177-83. Epub 2010 Mar 22.

Since RLS is common in rheumatologic disorders such as rheumatoid arthritis or Sjögren's syndrome, rheumatologists need to be familiar with the condition.

"Restless legs syndrome: a common disorder in patients with rheumatologic conditions." Hening WA, Caivano CK. Semin Arthritis Rheum. 2008 Aug;38(1):55-62. Epub 2007 Oct 30.

inflammation and disease
The purpose of this analysis was to investigate the prevalence and correlates of restless legs syndrome (RLS) symptoms in the 2005 National Sleep Foundation (NSF) Sleep in America 2005 Poll. The NSF poll is an annual telephone interview of a random, representative sample of US adults.

The NSF 2005 poll included 1,506 adults. Their mean age was 49 years, and 775 were women.

Symptoms of RLS that included unpleasant feelings in the legs for at least a few nights a week, which were worse at night, were reported by 9.7% of individuals in this poll, including 8% of men and 11% of women.

Adults who were at risk for RLS appeared to also be at increased risk for sleep apnea and insomnia (p < 0.05).


Phillips B, Hening W, Britz P, Mannino D. Prevalence and correlates of restless legs syndrome: results from the 2005 National Sleep Foundation Poll. Chest 2006;129:76-80.

An adult cohort with tuberous sclerosis complex was investigated for the prevalence of sleep disturbances and the relationship with seizure variables, medication, and psychological functioning. Information on 35 adults was gathered.

A subjective sleep disorder was found in 31% of the cohort. Insomnia scores showed a significant positive correlation with obstructive sleep apnea syndrome and restless legs syndrome scores.


"Characterizing sleep disorders of adults with tuberous sclerosis complex: a questionnaire-based study and review." van Eeghen AM, Numis AI, Staley BA, Therrien SE, Thibert RL, Thiele EA. Epilepsy Behav. 2011 Jan;20(1):68-74. Epub 2010 Dec 3.

inflammation and disease
Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are related sleep disorders that occur with increased frequency in spinal cord disease.

Our report describes a patient who developed RLS and PLMD after acute transverse myelitis associated with infectious mononucleosis, and failed to respond to intrathecal baclofen.


"Transverse myelitis associated with restless legs syndrome and periodic movements of sleep responsive to an oral dopaminergic agent but not to intrathecal baclofen." Brown LK, Heffner JE, Obbens EA. Sleep. 2000 Aug 1;23(5):591-4.

The spinal cord is involved in RLS pathophysiology because the muscles engaged in PLMS and RLS movements and receiving peripheral impulses for the sensory symptoms are controlled from the spinal part of the CNS. RLS can be induced by spinal cord lesion or spinal cord ischaemia and also by spinal anaesthesia. Patients suffering from RLS had significantly increased spinal cord excitability.

"Restless Legs Syndrome in 2004." Sonka K., Kemlink D. Prague Medical Report / Vol. 105 (2004) No. 4, p. 337–356

Our study shows that patients with RLS exhibit a profound static mechanical hyperalgesia to pin-prick stimuli, but no dynamic mechanical hyperalgesia (allodynia). This type of hyperalgesia is probably mediated by central sensitization to Adelta-fibre high-threshold mechanoreceptor input, a hallmark sign of the hyperalgesia type of neuropathic pain.

"Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome." Stiasny-Kolster K, Magerl W, Oertel WH, Möller JC, Treede RD. Brain. 2004 Apr;127(Pt 4):773-82. Epub 2004 Feb 25.

inflammation and disease
Several case studies have reported on restless legs syndrome (RLS) associated with stroke. In this study, we investigated the prevalence and the lesion topography of poststroke RLS.

There were 137 patients with ischemic stroke included in this study. The diagnosis of RLS was made 1 month after the index stroke using the criteria established by the International RLS Study Group. All patients enrolled underwent magnetic resonance imaging within 7 days of the onset of the stroke. The prevalence of stroke-related RLS was calculated, and the topography of the associated ischemic lesions was analyzed.

Stroke-related RLS was found in 10 out of 33 patients with a basal ganglia/corona radiata infarct (30.3%), 1 out of 8 patients with an internal capsular infarct (12.5%), and 1 out of 7 patients with a thalamic infarct (14.3%). In addition, one out of 54 with a cortical lesion with/ without subcortical involvement (1.9%), and 4 out of 18 patients with a pontine lesion (22.2%) had RLS.

The Prevalence of stroke-related RLS was 12.4% with a higher frequency in women. The occurrence of stroke-related RLS, noted in this study, is difficult to explain and can only be speculative at this point in time.


"Poststroke Restless Legs Syndrome and Lesion location: Anatomical Considerations." Seung-Jae Lee, MD, Joong-Seok Kim, MD, PhD,* In-Uk Song, MD, Jae-Young An, MD, Yeong-In Kim, MD, and Kwang-Soo Lee, MD. Movement Disorders, Vol. 24, No. 1, 2009

inflammation and disease
Gilles de la Tourette's syndrome (GTS) and restless legs syndrome (RLS) are two different neurological disorders with common features such as involuntary movements. In both disorders a disturbance of the dopaminergic system has been considered among other possible mechanisms. Since periodic leg movements (PLMS) during sleep are the predominant objective finding in RLS, the aim of this study was to investigate sleep parameters in GTS patients with particular emphasis on PLMS. Seven drug-free patients with GTS and seven age- and sex-matched healthy controls were studied polysomnographically, including superficial electromyogram (EMG) leads on all four extremities. A high number of PLMS were found in five of seven, and periodic arm movements in four of seven GTS patients. Total sleep time was significantly lower (P < 0.05) in the GTS patients than in the controls, which confirms earlier findings. The presence of PLMS in GTS might point towards evidence for a pathophysiological relationship between GTS and RLS, which, however, is not supported by the different responses to pharmacological treatments.

"Periodic limb movements during sleep are a frequent finding in patients with Gilles de la Tourette's syndrome." Voderholzer U, Müller N, Haag C, Riemann D, Straube A. J Neurol. 1997 Aug;244(8):521-6.


















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