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Re: Published Research - General Sleep and RLS

Posted: Tue Oct 16, 2012 2:41 am
by ViewsAskew
The Real Burden of Restless Legs Syndrome: Clinical and Economic Outcomes - Page 4
Rachel E. Salas, MD; and Anthony B. Kwan


A study from Philipps-University Marburg in Germany, published in 2010, utilized expenditure figures from a relatively transparent public/private insurance system. It should be noted that the study included data collected via a validated questionnaire given to 519 participants with RLS at various disease stages who were being seen at 5 different treatment centers. Direct and indirect costs were calculated for a 3-month period of observation. Costs were reported in 2006 Euros, and are converted here at a rate of 1.25 dollars per Euro, which was the average exchange rate in 2006 and is the approximate exchange rate in September 2012.23 Total 3-month costs were found to be $2613, of which 37% was attributed to direct costs. Three-month direct medical and non-medical costs for the health insurance provider were $974. The largest proportion of this cost, $443, was attributable to hospitalization, which was necessary in 32 patients who had an average length of stay of 1 day. Mean drug costs, which amounted to $374, comprised the second-largest direct cost category. Physician/outpatient services accounted for another $63, and physical therapy, $57. Indirect cost calculations were based on 3 categories—working days lost, productivity lost, and early retirement costs— and amounted to a total of $1635 during the 3-month period. Both direct and indirect costs were found to be significantly associated with disease severity (P <.01).23

A separate cost-of-illness study from Germany employed the Markov model to estimate annual RLS-related expenditures. The annual direct costs to a “sickness fund” (a type of non-profit health insurance provider which most Germans are obliged to join) were estimated to be $1237, while $1607 in costs were incurred outside the sickness fund system. Drug costs represented roughly two-thirds of expenditures.24 It should be noted that treatment costs, and to some extent drug costs, are typically lower in Germany than in the United States.

RLS expenditures, while not extraordinarily high, certainly represent meaningful expenditures both directly and indirectly. This was confirmed by a systematic review of cost studies in RLS, which, although heterogeneous in design and results, was consistent in observing higher rates of expenditure for third-party payers for patients with RLS compared with average patients without RLS in the primary care setting. The review also found that pharmacologic treatment of RLS was consistently cost-effective across therapies.25

The full economic impact of not treating RLS has not been satisfactorily evaluated at present. Nevertheless, it seems highly likely that certain costs—for example, lost productivity, which already comprises a very substantial part of the total costs related to RLS—will increase when patients experience greater disease severity. It may also be the case that failure to treat RLS exacerbates comorbidities, requiring additional expenditures and healthcare resource utilization that might not otherwise be necessary.


RLS is an underdiagnosed condition with a relatively high prevalence and a negative effect on QoL. The deleterious impact of RLS on QoL is perhaps surprisingly large for a condition that may not appear particularly serious to those unfamiliar with it. The effects of RLS can be very serious indeed, and QoL among its sufferers is generally worse than that of other chronic diseases such as type 2 diabetes, depression, and osteoarthritis. Sleep disturbance, perhaps more than any other feature of RLS, is responsible for a large proportion of the deterioration in QoL associated with the condition and represents a cardinal feature of RLS. RLS is also associated with a spectrum of comorbidities, including renal disease, hypertension, and fibromyalgia. The costs, both direct and indirect, attributable to RLS are substantial, and although recent analyses of the economic impact of RLS do not address nationwide costs, they are likely to be significant considering both the measurable costs on an individual basis and the extent of the prevalence of RLS. Greater awareness among clinicians and managed care professionals about RLS has the potential to help improve rates of diagnosis and treatment, which will potentially reduce the impact of RLS on patient QoL and healthcare expenditures.

Author affiliation: Undergraduate Neuroscience Program, Johns Hopkins University, Baltimore, MD (ABK); Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (RES).
Funding source: This supplement was supported by UCB, Inc.
Author disclosure: Anthony B. Kwan and Rachel E. Salas, MD, report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this supplement.
Authorship information: Concept and design (ABK); acquisition of data (ABK); drafting of the manuscript (ABK, RES); critical revision of the manuscript for important intellectual content (RES); and supervision (RES).
Address correspondence to: Rachel E. Salas, MD, Johns Hopkins School of Medicine, 601 N Wolfe, Meyer 6119, Baltimore, MD 21287. E-mail:

Allen RP, Bhamal M, Calloway M. Prevalence and disease burden of primary restless legs syndrome: results of a general population survey in the United States. Movement Disorders. 2011;26(1):114-120.
Allen RP, Walters AS, Montplaisir J, et al. Restless legs syndrome prevalence and impact–REST general population study. Arch Intern Med. 2005;165:1286-1292.
Hening WA, Allen RP, Washburn M, Lesage SR, Earley CJ. The four diagnostic criteria for Restless Legs Syndrome are unable to exclude confounding conditions (“mimics”). Sleep Med. 2009;10(9):976-981.
Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. Sleep Med. 2003;4:101-119.
Ekbom K, Ulfberg J. Restless legs syndrome. J Intern Med. 2009;266:419-431.
Innes KE, Selfe TK, Agarwal P. Prevalence of restless legs syndrome in North American and Western European populations: a systematic review. Sleep Med. 2011;12(7):623-634.
Szentkiralyi A, Fendrich K, Hoffmann W, Happe S, Berger K. Socio-economic risk factors for incident restless legs syndrome in the general population [published online ahead of print February 27, 2012]. J Sleep Res.
Kushida C, Martin M, Nikam P, et al. Burden of restless legs syndrome on health-related quality of life. Qual Life Res. 2007;16:617-624.
Abetz L, Allen R, Follet A, et al. Evaluating the quality of life of patients with restless legs syndrome. Clin Ther. 2004;26(6):925- 935.
Hening W, Walters AS, Allen RP, Montplaisir J, Myers A, Ferini-Strambi L. Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study. Sleep Med. 2004;5(3):237-246.
Lichstein KL, Durrence HH, Taylor DJ, et al. Quantitative criteria for insomnia. Behav Res Ther. 2003;41:427-445.
Winkelmann J, Wetter TC, Collado-Seidel V, et al. Clinical characteristics and frequency of the hereditary restless legs syndrome in a population of 300 patients. Sleep. 2000;23:597-602.
Salas RE, Rasquinha R, Gamaldo CE. All the wrong moves: a clinical review of restless legs syndrome, periodic limb movements of sleep and wake, and periodic limb movement disorder. Clin Chest Med. 2010;31(2):383-395.
Gamaldo CE, Earley CJ. Restless legs syndrome: a clinical update. Chest. 2006;130:1596-1604.
Angelini M, Negrotti A, Marchesi E, Bonavina G, Calzetti S. A study of the prevalence of restless legs syndrome in previously untreated Parkinson’s disease patients: absence of co-morbid association. J Neurol Sci. 2011;310(1-2):286-288.
Scholz H, Benes H, Happe S, et al. Psychological distress of patients suffering from restless legs syndrome: a cross-sectional study. Health Qual Life Outcomes. 2011;9:73-79.
Merlino G, Piani A, Dolso P, et al. Sleep disorders in patients with end-stage renal disease undergoing dialysis therapy. Nephrol Dial Transplant. 2006;21(1):184-190.
Giannaki CD, Sakkas GK, Karatzaferi C, et al. Evidence of increased muscle atrophy and impaired quality of life parameters in patients with uremic restless legs syndrome. PLoS One. 2011;6(10):e25180.
Batool-Anwar S, Malhotra A, Forman J, Winkelman J, Li Y, Gao X. Restless legs syndrome and hypertension in middle-aged women. Hypertension. 2011;58(5):791-796.
Viola-Saltzman M, Watson NF, Bogart A, Goldberg J, Buchwald D. High prevalence of restless legs syndrome among patients with fibromyalgia: a controlled cross-sectional study. J Clin Sleep Med. 2010;6(5):423-427.
Stehlik R, Arvidsson L, Ulfberg J. Restless legs syndrome is common among female patients with fibromyalgia. Eur Neurol. 2009;61(2):107-111.
Basu PP, Shah NJ, Krishnaswamy N, Pacana T. Prevalence of restless legs syndrome in patients with irritable bowel syndrome. World J Gastroenterol. 2011;17(39):4404-4407.
Dodel R, Happe S, Peglau I, et al. Health economic burden of patients with restless legs syndrome in a German ambulatory setting. Pharmacoeconomics. 2010;28(5):381-393.
Nelles S, Köberlein J, Grimm C, Pittrow D, Kirch W, Rychlik R. Socioeconomic relevance of the idiopathic restless legs syndrome (RLS) in Germany: cost-of-illness study. Med Klin (Munich). 2009;104(5):363-371.
Reinhold T, Müller-Riemenschneider F, Willich SN, Brüggenjürgen B. Economic and human costs of restless legs syndrome. Pharmacoeconomics. 2009;27(4):267-279.

Re: Published Research - General Sleep and RLS

Posted: Sun Dec 02, 2012 5:49 am
by ViewsAskew
Well, not the news we'd hope for, but also nothing really new. Many women already know this. And for all I know one of us already found this and I'm repeating it, since it's from 2010. But, it refreshes our memories :-). ... m7KvQ.cspx

Home : News : Health News : Restless Leg Syndrome (RLS)
Restless Legs Syndrome in Pregnancy Linked to Later Risk
Study Shows Higher Risk of Chronic RLS for Women Who Had Condition in Pregnancy

WebMD Medical News

By Katrina Woznicki

Reviewed by Laura J. Martin, MD

Dec. 6, 2010 -- Women who had restless legs syndrome (RLS) while pregnant were four times more likely to have the condition again after their pregnancies, and were three times more likely to have the chronic form of the condition, according to a small European study.

Researchers led by Mauro Manconi, MD, PhD, from Vita-Salute University in Milan, Italy, and colleagues compared 74 women who had experienced restless legs syndrome during their pregnancies and 133 women who had not.

Restless legs syndrome is a neurological disorder characterized by uncomfortable sensations in the legs that sometimes lead to a feeling of needing to move the legs for relief. Symptoms are often worse during the night. The disorder affects about 10% of the U.S. population.

Symptoms of restless legs syndrome can arise during pregnancy and then disappear after childbirth. The incidence of restless legs syndrome among pregnant women ranges from 26% to 30% and often peaks during the third trimester, according to the researchers.
RLS During and After Pregnancy

Study participants were surveyed and asked about their medical history, including symptoms of restless legs syndrome and medications they used within two days after delivery. The women were then followed for an average of 6.5 years to see who developed recurrent restless legs syndrome.

The researchers found that:

24% of women who had restless legs syndrome during pregnancy had the disorder at the end of the study, compared with 8% of women who did not have the syndrome while pregnant.
58% of women who reported restless legs syndrome symptoms while pregnant experienced symptoms again in a future pregnancy, compared with 3% of women who did not have the disorder during a first pregnancy.
The incidence of developing the chronic form of restless legs syndrome was 34.4 per 1,000 in the pregnancy-related restless leg syndrome group compared 11.5 per 1,000 among those who did not experience restless legs syndrome during pregnancy.

The study results suggest pregnancy-related restless legs syndrome may signal a risk for developing future transient episodes or even the chronic form of the disorder.

The findings are published in the Dec. 7 issue of Neurology.

“This is the first long-term study to look at a possible connection between restless legs syndrome in pregnancy and repeat occurrences in later years or future pregnancies,” writes study researcher Mauro Manconi, MD, PhD, with Vita-Salute University in Milan, Italy. “Most of the time, when a woman experiences RLS in pregnancy, it disappears after the baby is born. However, our results show that having the condition during pregnancy is a significant risk factor for a future chronic form or the short-term form in other pregnancies down the road. Women who experience RLS should still be reassured that symptoms will probably disappear after delivery but may reappear later on.”

Re: Published Research - General Sleep and RLS

Posted: Mon Dec 03, 2012 5:49 am
by badnights
I've seen that before, but I can't remember where - whether here or somewhere else. For the second time, I refrained from forwarding it to my sister. She got RLS/WED during all three of her pregnancies. But I have to let her live without worrying about it.

Re: Published Research - General Sleep and RLS

Posted: Tue Dec 04, 2012 4:09 am
by ViewsAskew
Now we're getting somewhere! More research that the limbic system is involved. Still no idea why, but more differences between non-WED and WED patients, this time in the thalamus. ... hort?rss=1

Abnormal medial thalamic metabolism in patients with idiopathic restless legs syndrome

Giovanni Rizzo1,2,3,; Caterina Tonon1; Claudia Testa1; David Manners1,4; Roberto Vetrugno3; Fabio Pizza2,3; Sara Marconi2,3; Emil Malucelli1; Federica Provini2,3; Giuseppe Plazzi2,3; Pasquale Montagna3,* and Raffaele Lodi1

+ Author Affiliations

1 Functional MR Unit, Department of Internal Medicine, Aging and Nephrology, University of Bologna, Bologna, Italy
2 IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
3 Department of Neurological Sciences, University of Bologna, Bologna, Italy
4 Department of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy

Correspondence to: Raffaele Lodi, MD, PhD, Department of Internal Medicine, Aging and Nephrology, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy E-mail:

Received May 18, 2012.
Revision received July 30, 2012.
Accepted August 14, 2012.


Pathophysiology of restless legs syndrome is poorly understood. A role of the thalamus, specifically of its medial portion which is a part of the limbic system, was suggested by functional magnetic resonance imaging and positron emission tomography studies. The aim of this study was to evaluate medial thalamus metabolism and structural integrity in patients with idiopathic restless legs syndrome using a multimodal magnetic resonance approach, including proton magnetic resonance spectroscopy, diffusion tensor imaging, voxel-based morphometry and volumetric and shape analysis. Twenty-three patients and 19 healthy controls were studied in a 1.5 T system. Single voxel proton magnetic resonance spectra were acquired in the medial region of the thalamus. In diffusion tensor examination, mean diffusivity and fractional anisotropy were determined at the level of medial thalamus using regions of interest delineated to outline the same parenchyma studied by spectroscopy. Voxel-based morphometry was performed focusing the analysis on the thalamus. Thalamic volumes were obtained using FMRIB's Integrated Registration and Segmentation Tool software, and shape analysis was performed using the FMRIB Software Library tools. Proton magnetic resonance spectroscopy study disclosed a significantly reduced N-acetylaspartate:creatine ratio and N-acetylaspartate concentrations in the medial thalamus of patients with restless legs syndrome compared with healthy controls (P < 0.01 for both variable). Lower N-acetylaspartate concentrations were significantly associated with a family history of restless legs syndrome (β = −0.49; P = 0.018). On the contrary, diffusion tensor imaging, voxel-based morphometry and volumetric and shape analysis of the thalami did not show differences between the two groups. Proton magnetic resonance spectroscopic findings in patients with restless legs syndrome indicate an involvement of medial thalamic nuclei of a functional nature; however, the other structural techniques of the same region did not show any changes. These findings support the hypothesis that dysfunction of the limbic system plays a role in the pathophysiology of idiopathic restless legs syndrome.

Re: Published Research - General Sleep and RLS

Posted: Tue Dec 04, 2012 11:52 am
by cornelia
Gosh, difficult to read, but exciting. However, it gives me the feeling that we are way off finding a solution. Guess that is normal.


Re: Published Research - General Sleep and RLS

Posted: Tue Dec 04, 2012 7:47 pm
by ViewsAskew
Yes, difficult to read! I agree, Corrie, that it seems we have a long way to go. I'm so happy that this is another bit of the puzzle and every bit counts.

Re: Published Research - General Sleep and RLS

Posted: Fri Dec 07, 2012 5:56 am
by badnights
I'm glad there are people looking at something besides the dopamine systems.

Re: Published Research - General Sleep and RLS

Posted: Wed Dec 12, 2012 9:14 pm
by ViewsAskew
And, another group looking at something besides the dopamine system. ... ast=Shukla

Quantitative thermal sensory testing and sympathetic skin response in primary Restless legs syndrome - A prospective study on 57 Indian patients

Garima Shukla, Vinay Goyal, Achal Srivastava, Madhuri Behari
Department of Neurology, All India Institute of Medical Sciences, New Delhi, India

Patients with restless leg syndrome present with sensory symptoms similar to peripheral neuropathy. While there is evidence of abnormalities of dopaminergic pathways, the peripheral nervous system has been studied infrequently. We studied conventional nerve conduction studies, quantitative thermal sensory testing and sympathetic skin response in 57 patients with primary restless leg syndrome. Almost two third patients demonstrated abnormalities in the detailed testing of the peripheral nervous system. Sbtle abnormalities of the peripheral nervous system may be more common than previously believed.

Patients with restless legs syndrome (RLS) present with predominantly sensory manifestations, which often resemble and sometimes are mistaken as those of peripheral neuropathy. Although there is ample evidence for involvement of dopaminergic pathways as well as iron metabolism in the etiopathogenesis of RLS, there are several unanswered questions in this area, and there is not yet much literature on involvement of the peripheral nervous system in patients with RLS. Moreover, a large proportion of patients with peripheral neuropathy of varied etiology may have a combination of neuropathic symptoms as well as RLS. We conducted this study to assess the prevalence of electrophysiological and psychophysiological evidence of involvement of small peripheral nerve fibers in consecutive patients of primary RLS, using quantitative thermal sensory testing, sympathetic skin response, and nerve conduction studies.

Materials and Methods
Over a period of 3 years from October 2003 to September 2006, all consecutive patients who presented to the sleep disorders clinic, neurology services at the All India Institute of Medical Sciences, fulfilling the IRLSSG criteria of RLS, [1] were evaluated in detail. Patients were interrogated for details of clinical phenomena involving limbs, their duration, intensity, aggravating and relieving factors, diurnal pattern of occurrence for association with other medical or neurological illnesses, drug history, and response to dopamine agonists through a pre-structured performa. All patients underwent investigation for detailed hematological and biochemical profile, mainly for evidence of anemia, low ferritin levels for hepatic or renal impairment. All patients with RLS, thus diagnosed, without any clinical evidence of or family history of peripheral neuropathy formed the study population. Patients with pregnancy or any medical, hematological, or neurological disorders, known as secondary causes of RLS, were excluded. After detailed clinical evaluation and assessment of severity by the RLS rating scale, [2] patients were subjected to nerve conduction studies on upper limb and lower limb on one side, followed by examination with quantitative thermal sensory testing (QST) by method of limits. [3] Routine nerve conduction studies, carried out on a Medelec Synergy Ò EMG/EP system, included motor conduction and F-wave studies for Median, Ulnar, common peroneal and posterior tibial nerves and sensory conduction studies for Median, Ulnar, and Sural nerves on one side in patients with symmetrical distribution of symptoms and evaluation of a third limb in patients with asymmetrical symptoms. The sympathetic skin response (SSR) was tested for in all patients, with assessment using electrode placement over an upper limb and the ipsilateral lower limb.

QST was carried out using a Medoc TSA-II Neurosensory analyzer at one or more sites, with method of Limits. Subjects were seated comfortably, on a chair in a quiet room, with ambient temperature of 24°-25° Celsius. The site used for testing the lower limb was dorsolateral border of foot, and the site used in the upper limb was the hypothenar eminence. The modalities tested were cold sensation and warm sensation. Patients were instructed in detail, the nature of the test and the need to react attentively and promptly to change in temperatures. The test was performed by placing a 30 mm × 30 mm thermode over the skin of the site to be tested, and averages of 4 readings of threshold temperature for each sensory modality were noted. Note was also made if the modality was identified incorrectly. Based on values obtained from the control population, previously reported, the mean threshold temperature ± 2 SD for each modality was considered as the upper (or lower) limit of normal.

A total of 105 patients (52 males, 53 females) with RLS were seen from September 2003 to August 2006. Among these, 57 patients (38 females, 19 males) with an average age of 43 ± 14.5 years could be classified as primary RLS. The average duration of symptoms in lower limbs was 5.4 years. All patients revealed no abnormality on detailed medical and neurological examination. Current drug treatment included dopamine agonists (57 patients), Clonazepam (2 patients), Topiramate for migraine (5 patients), SSRIs (5 patients), and oral iron (3 patients) [Table 1].

Table 1: Clinical details of patients with primary RLS(n = 57) LINK TO TABLE

Nerve conduction studies were found normal in all patients. QST could be performed in 50 patients and revealed abnormal thresholds for both sensations in lower limbs and for at least one modality of sensation (cold or warm) in upper limbs in 33 patients (66%). Fifteen patients (30%) among these (all of whom had abnormalities on QST) also showed a non-recordable SSR, both on upper limb and lower limb recordings.

Thermal thresholds
The average cold sensation thresholds among patients over the foot (dorsolateral) site were 26.77 ± 5.51 while over the palmar (hypothenar) site were 27.72 ± 2.7. The average warm sensation threshold over the foot site was 37.97 ± 4.23 and 37.67 ± 4.53. .

Table 2: Thermal thresholds in patients with RLS as compared with those in normal controls LINK TO TABLE

This study is among the few studies in which thermal threshold abnormalities have been studied for and identified. This is the largest study till now with 57 patients suffering from primary RLS, studied with quantitative assessment of thermal sensory abnormalities, and nearly 66% patients were observed to manifest with significant abnormalities.

We included 37 female and 19 male patients in the age group of 43 ± 14 years. Our patients had fairly long standing symptoms with an average duration of about 5 years. We had meticulously excluded conditions, which could be associated with secondary RLS. Nerve conduction studies conducted on all patients revealed no abnormalities. In one of the earliest of the few studies, addressing the subject of peripheral nerve involvement in patients with primary RLS, Iannaconne S et al. examined 8 consecutive patients. All known causes for peripheral neuropathy and other neurological abnormalities were ruled out. The age and sex distribution was similar to that in our study. In this study also, nerve conduction studies were normal in all patients. [4] In another study by Polydefkis M et al. on 22 consecutive patients presenting with RLS, one among whom already had symptoms of large fiber peripheral neuropathy, 5 patients were detected to have abnormal Sural sensory nerve action potential amplitudes. Also, 3 patients, who clearly had unilateral radicular symptoms and backache, were found to have reduced deep peroneal compound muscle action potential amplitudes. [5] The patients included in this study were older (average age 62.2 ± 5.9). They did not exclude patients with known peripheral neuropathy or clinical features of neuropathy although patients with any comorbid illness like diabetes, uremia, and Vit B12 deficiency were excluded. The less stringent inclusion criteria possibly account for the observation of abnormal lower limb sensory conduction abnormalities, which may also not necessarily be suggestive of presence of large fiber neuropathy considering the older age group of the patients.

In their review on secondary RLS, Ondo W reported electrophysiologic evidence of neuropathy using standard EMG/NCV techniques in 37/98 (36.6%) of RLS patients; most having mild-to-moderate sensory axonal neuropathies of diverse etiology. The presence of neuropathy was much higher in patients who did not have a family history, compared with those who did have a family history: 22/31 (71%) vs. 15/67 (24%), P < 0.001. [6] These observations are valuable; however, since we carefully included patients with primary RLS, excluding all patients with any identifiable secondary causes, comparison would be improbable.

We observed abnormalities in at least one modality on quantitative thermal sensory testing among 66% of patients examined in this study. Schattschneider S et al. found abnormalities in thermal thresholds in 72% patients with secondary RLS (n = 22) and 55% patients with idiopathic RLS (n = 20). In addition to the QST, they also examined peripheral C fiber function with quantitative nerve axon reflex testing (QNART) and found no abnormalities in this among patients with primary RLS as compared to significant abnormalities among patients with secondary RLS. The authors attribute these differences to abnormal central somatosensory processing among patients with primary RLS while these are attributed to small fiber neuropathy in patients with secondary RLS. [7] In a recent study, 21 patients with primary RLS were compared with 13 patients with secondary RLS (with co-existent small fiber neuropathy confirmed by skin biopsy) and 20 normal controls, the patients with primary RLS showed hyperalgesia to blunt pressure, pinprick, and vibratory hyperesthesia while patients with secondary RLS, associated with small fiber neuropathy, showed thermal hypoesthesia to cold (A delta-fiber mediated) and warm (C-fiber mediated) and hyperalgesia to pinprick. [8] These authors conclude that static mechanical hyperalgesia in primary and secondary restless legs syndrome is consistent with the concept of central disinhibition of nociceptive pathways, which might be induced by conditioning afferent input from damaged small fiber neurons in secondary restless legs syndrome. None of our patients had symptoms of small fiber neuropathy, yet abnormalities on thermal thresholds were observed in a sizeable proportion of patients similar to that observed in these 2 studies discussed. Our limitation was inability to perform any further investigations to localize the level of involvement within the sensory pathways. This work, however, should form a basis for further investigation into the prevalence of small fiber neuropathy among patients diagnosed with primary RLS and also confirm findings observed by these investigators in small number of patients. It is possible that even among patients with primary RLS, who do not progress into overt small or large fiber neuropathy, there are abnormalities in the peripheral nervous system as shown by Iannaconne et al. [4]

Lastly, we also observed the sympathetic skin response, a non-specific tool to assess integrity of the sympathetic nervous system, to be abnormal among 30% of patients studied. This has not been reported yet in any previous studies. This observation in conjunction with thermal threshold abnormalities might also strengthen the possibility of involvement of the small unmyelinated fibers within the peripheral nervous system, especially since previous investigators have found almost similar findings as ours among patients with primary RLS.

This study reveals that a large proportion, almost two-thirds, of patients with primary RLS demonstrates abnormal thermal thresholds and SSR with a possibility of significantly prevalent abnormalities of small peripheral nerve fibers.

1. Allen RP, Hening WA, Montplaisir J, Picchietti D, Trenkwalder C, Walters AS; Restless Legs Syndrome Diagnosis and Epidemiology workshop at the National Institutes of Health; International Restless Legs Syndrome Study Group. Restless legs syndrome: Diagnostic criteria, special considerations, and epidemiology: A report from the RLS diagnosis and epidemiology workshop at the national institute of health. Sleep Med 2003;4:101-19. Back to cited text no. 1

2. Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, et al. International Restless Legs Syndrome Study Group. Validation of the International restless legs syndrome study group rating scale for restless legs syndrome. Sleep Med 2003;4:121-32. Back to cited text no. 2
3. Yarnitsky D. Quantitative sensory testing. Muscle Nerve 1997;20:198-204. Back to cited text no. 3
4. Iannaccone S, Zucconi M, Marchettini P, Ferini-Strambi L, Nemni R, Quattrini A, et al. Evidence of peripheral axonal neuropathy in primary restless legs syndrome. Mov Disord 1995;10:2-9. Back to cited text no. 4
5. Polydefkis M, Allen RP, Hauer P, Earley CJ, Griffin JW, McArthur JC. Subclinical sensory neuropathy in late-onset restless legs syndrome. Neurology 2000;55:1115-21. Back to cited text no. 5
6. Ondo W. Secondary Restless legs syndrome. In: Chaudhari KR, Odin R, Olanow CW, editors. Restless legs syndrome. London and New York: Taylor& Francis; 2009;p. 57-84. Back to cited text no. 6

7. Schattschneider J, Bode A, Wasner G, Binder A, Deuschl G, Baron R. Idiopathic restless legs syndrome: Abnormalities in central somatosensory processing. J Neurol 2004;251:977-82. Back to cited text no. 7
8. Bachmann CG, Rolke R, Scheidt U, Stadelmann C, Sommer M, Pavlakovic G, et al. Thermal hypoaesthesia differentiates secondary restless legs syndrome associated with small fibre neuropathy from primary restless legs syndrome. Brain 2010;133(Pt 3):762-70.

Re: Published Research - General Sleep and RLS

Posted: Thu Dec 13, 2012 12:13 am
by Polar Bear
This article is soooooooooo.... interesting.
I find this ringing a bell.

Re: Published Research - General Sleep and RLS

Posted: Sun Dec 16, 2012 6:40 am
by badnights
some like it hot, and some like it cold

Re: Published Research - General Sleep and RLS

Posted: Sun Dec 16, 2012 10:32 pm
by ViewsAskew
ViewsAskew wrote: Conclusion
This study reveals that a large proportion, almost two-thirds, of patients with primary RLS demonstrates abnormal thermal thresholds and SSR with a possibility of significantly prevalent abnormalities of small peripheral nerve fibers.

So many of us really dislike being touched or close to things - this may help explain it.

Re: Published Research - General Sleep and RLS

Posted: Sat Feb 09, 2013 7:33 pm
by badnights
This is a beauty, found by a friend of mine doing a google search. It is buried without links on the RLSF website. It's a slide show by Arthur Walters, an RLS/WED specialist, in which he summarizes many unconventional treatments for RLS/WED. He gives references for many of them too. The latest reference cited is 2008, so the presentation probably dates from 2008 or 2009. I had no idea so much was being done!

Access it through this link
or by downloading this:
A presentation prepared by Dr. Walters (in 2008 or 2009??) on less-conventional (mostly experimental) treatments for RLS/WED
(1.52 MiB) Downloaded 115 times

Re: Published Research - General Sleep and RLS

Posted: Sat Feb 09, 2013 10:11 pm
by ViewsAskew
I really wish the Foundation could afford to have the conferences that they used to hold. They were funded, in part, by pharma and that was perceived to be an issue. So, they stopped them. Each year, I'd see all this kind of research and get to hear everything going on. I miss that.

Wouldn't it be nice if some of these researchers had a way to provide us with this kind of information on a regular basis?

Re: Published Research - General Sleep and RLS

Posted: Sun Feb 10, 2013 12:50 am
by badnights
I was going to see if I could find an email for him after I posted, but I got side-tracked.

That is one thing I would love to see on the foundation web page - a regularly updated list of links - or btter, summaries of - recent research.

Re: Published Research - General Sleep and RLS

Posted: Sun Feb 10, 2013 9:00 pm
by badnights
Dissociation of periodic leg movements from arousals in restless legs syndrome
Mauro Manconi; Raffaele Ferri; Marco Zucconi; Claudio L Bassetti; Stephany Fulda; Debora Aricò; Luigi Ferini-Strambi
Ann. Neurol. 71, 834 (2012)
Sleep and Epilepsy Center, Neurocenter of the Southern Switzerland, Civic Hospital of Lugano, Via Tesserete 46, Lugano, Switzerland.

OBJECTIVE: The purpose of this study was to characterize the nature of the relation between periodic leg movements during sleep (PLMS) and cortical arousals to contribute to the debate on the clinical significance and treatment of PLMS.

METHODS: A prospective, placebo-controlled, single-blind, parallel group study was carried out including 46 drug-naive patients with idiopathic restless legs syndrome (RLS). Each patient underwent 2 consecutive full-night polysomnographic studies. The first night was the baseline night. Prior to the second night, 1 group received a single oral dose of 0.25mg pramipexole, whereas a second group received a single oral dose of 0.5mg clonazepam, and the remaining patients received placebo. Sleep stages, cyclic alternating pattern (CAP), and leg movement activity were scored following standard criteria; symptoms of RLS were also assessed.

RESULTS: Pramipexole suppressed PLMS without affecting electroencephalographic (EEG) instability (CAP) and arousals (corresponding to CAP A3 and, partially, A2 subtypes), whereas clonazepam did the opposite, reducing non-rapid eye movement sleep EEG instability without effects on PLMS. Both drugs were effective on sensory RLS symptoms.

INTERPRETATION: This study demonstrates that a selective pharmacological approach can disconnect PLMS from arousal events, suggesting an indirect relation between each other. These results might weaken the hypothesis of a direct pathological role of PLMS in sleep disruption and can be important for the discussion on the existence of a distinct entity called periodic limb movements disorder. Moreover, the study opens the doors to the possibility of a joint treatment for RLS targeting sensory and motor symptoms, as well as sleep instability.