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Posted: Tue Dec 04, 2007 5:05 am
by ViewsAskew
This is an abstract that seems to be telling us that we have no worries that there is any relation to PD or a real problem with our dopaminergic system. Obviously, there is a problem, but not an underlying degenerative disease. ... D=20067542

INTRODUCTION: Low-dose apomorphine challenge has been shown to cause a rise in growth hormone (GH) in patients with Parkinson's disease (PD). This was interpreted as an increased postsynaptic sensitivity of hypothalamic dopamine receptors in the course of a generalized degeneration of dopaminergic neurons. The dopaminergic system in the restless legs syndrome (RLS) has been assumed to play a role in its pathophysiology. It is therefore the aim of this study to determine whether the GH response to subcutaneously applied low-dose apomorphine is generally altered in patients with RLS as compared to healthy controls. PATIENTS AND METHODS: We examined 40 patients with idiopathic RLS as well as 20 age- and sex-matched healthy control subjects by means of the low-dose apomorphine test. GH was analyzed at baseline, as well as 45 and 60 min after subcutaneous low-dose apomorphine injection in the morning. RESULTS: Forty RLS patients (58.3+/-11.9 years, 32 females) with a mean RLS severity scale score of 23.9+/-6.6 (range 10-37) were examined. GH was not significantly increased 45 and 60 min after injection (p=0.397) (2.44+/-2.35 ng/ml at baseline versus 2.71+/-2.29 ng/ml after 45 min and 2.18+/-1.83 ng/ml after 60 min). The results were independent of pre-treatment with levodopa. Age, sex, duration, and severity of the disease did not show a covariate effect with GH levels. There was no difference compared with healthy controls. CONCLUSIONS: RLS patients did not show an increase in GH after stimulation with low-dose apomorphine. Lack of sensitivity alteration of extrastriatal hypothalamic dopamine receptors suggests that RLS is not a general dopaminergic degenerative disease or might only show circadian alterations.

Posted: Tue Dec 04, 2007 5:07 am
by ViewsAskew
For those of you with pain....this is very interesting. Has anyone who has a LOT of pain ever been evaluated for this disoder - somatoform pain? ... D=20067551

Patients with somatoform pain often complain of sleep disorders, but sleep disorders are not an integrated part of the diagnosis of this disorder. Restless legs syndrome is associated with painful symptoms and sleep disturbances. The aim of our study was to evaluate the prevalence of restless legs syndrome (RLS) in somatoform pain disorder. METHOD: In this study 100 consecutive patients (mean age: 46.4; SD: 11.4; women: 58) diagnosed with somatoform pain disorder (SPD) were clinically investigated for the occurrence of RLS at the behavioral medicine clinic for pain outpatients in the department of psychiatry within the Medical University of Vienna. The pain parameters of SPD were assessed using a pain questionnaire and visual analogue scales (VAS). The severity of RLS was established using the questionnaire of the International Restless Legs Syndrome Study Group (IRLSSG). RESULTS: The prevalence of restless legs syndrome found in somatoform pain disorder was 42%. Interrupted sleep was found in 83.3% in somatoform pain disorder with comorbid RLS and in 64.1% in somatoform pain disorder without RLS. Patients with continuous somatoform pain had a significant higher occurrence of RLS (Sample: 55%; with RLS: 71.4% and without RLS: 43.1%). The pain parameters increased parallel to the severity of RLS. Additionally, RLS was associated with higher psychosocial disability in family life. CONCLUSIONS: The prevalence of RLS is high in our sample of patients with somatoform pain disorder. There seems to be a difference in pain profile between patients with and without RLS. RLS may increase the pain level and prolong pain in somatoform pain disorder. RLS should be considered when a somatoform pain disorder is diagnosed.

Posted: Tue Dec 04, 2007 6:20 am
by ViewsAskew
RLS resolution with compression (I thought I posted this awhile back, but didn't see it...could have it in a different post). But, it's worth posting twice as it's a great way to resolve RLS for some without drugs. ... D=20067956

Restless legs syndrome (RLS) is a common disorder that presents with irresistible urges to move the legs and motor restlessness, worsening in the evening. RLS commonly causes insomnia and associated daytime symptoms. Treatment of first choice for RLS is usually medication, but medications are often ineffective or poorly tolerated. An effective nonpharmacologic therapy would be highly desirable. Here we review RLS and its treatment and present data from a pilot study on the effect of a novel treatment for this condition. The objective of this study was to determine the therapeutic effect of pneumatic sequential compression devices (SCDs) on RLS symptoms.We performed an uncontrolled, prospective interventional study using SCDs on a convenience sample of adults reliably diagnosed with RLS. Patients were asked to wear the SCD for an hour each evening before the usual time of onset of restless legs symptoms. Before and after 1-3 months of SCD therapy, patients completed validated questionnaires to assess RLS severity, daytime sleepiness, and impact of RLS on quality of life in the domains of social function, daily task function, sleep quality, and emotional well-being. Compliance with SCD therapy was measured using patient-recorded logs.Of 10 patients (7 women; age range, 37-80 yr; mean age, 56 yr), symptomatic for a mean of 68 months (range, 12-360 mo), 1 could not tolerate wearing the SCD and withdrew from the protocol after 3 days. The remaining 9 patients complied with therapy 58%-100% of nights (mean, 82%). Three patients experienced complete resolution of RLS and 6 patients had improvement of symptoms. Group severity score improved from 24/40 to 8/40 (p = 0.001). Epworth Sleepiness Scale score improved from 12/24 to 8/24 (p = 0.05). Every quality of life score improved: social function from 74% to 96% (p = 0.04), daily task function 63% to 80% (p = 0.05), sleep quality 27% to 63% (p = 0.003), and emotional well-being from 49% to 83% (p = 0.02). In this group of patients, wearing the SCD in the evening for an hour improved symptoms of RLS and improved quality of life, with complete resolution of symptoms in 3 of 10 patients.

Posted: Fri Dec 28, 2007 7:59 pm
by ViewsAskew
This shows how much sleep affects the rest of our lives.... ... D=20068019

Posted: Fri Dec 28, 2007 8:17 pm
by ViewsAskew
Hmmm...many unanswered questions in this one for me. Who were the participants (genetic RLSers or origin unknown)? What "type" and degree of RLS did they have (painful, non-painful, 24/7)? Why was the sample size so small (hard to make any conclusions from such small number of participants)? And, what, if anything, does this research mean?

It does, however, lend some credence to those who undergo vein therapy getting results. Sadly, this doesn't happen to everyone, just a certain percent. But, maybe it's related... ... D=20068089

Posted: Fri Dec 28, 2007 8:19 pm
by ViewsAskew
This study surprised me! There really was a difference between generic and orignal drugs! They were only testing sleep drugs, but that doesn't bode well for other ones, either, does it? ... D=20068035

Posted: Fri Feb 29, 2008 10:58 pm
by ViewsAskew

About the genetic component - possibility of two locations on the gene

Evidence for linkage of restless legs syndrome to chromosome 9p
Are there two distinct loci?
K. Lohmann-Hedrich, PhD, A. Neumann, BS, A. Kleensang, MS, T. Lohnau, BS, H. Muhle, MD, A. Djarmati, PhD, I. R. König, PhD, P. P. Pramstaller, MD, E. Schwinger, MD, P. L. Kramer, PhD, A. Ziegler, PhD, U. Stephani, MD and C. Klein, MD
From the Department of Neurology (K.L.-H., A.N., T.L., A.D., C.K.), Institute of Medical Biometry and Statistics (A.K., I.R.K., A.Z.), and Department of Human Genetics (E.S.), University at Lübeck, Lübeck, Germany; Department of Neuropediatrics, University of Kiel, Kiel, Germany (A.N., H.M., U.S.); Institute of Genetic Medicine, EURAC Research, Bolzano, Italy (P.P.P.); and Department of Neurology, Oregon Health and Sciences University, Portland, OR (P.L.K.).

Address correspondence and reprint requests to Dr. Christine Klein, Department of Neurology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany

Background: Restless legs syndrome (RLS) is a common sensory-motor disorder characterized by paresthesias and an intense urge to move the legs with a considerable familial aggregation. To date, no gene mutation has been found, but five gene loci have been mapped in primary RLS to chromosomes 12q, 14q, 9p, 2q, and 20p (RLS1 through 5).

Patients/Methods: We identified a four-generational German RLS family with 37 family members including 15 affected cases. We performed linkage analysis using microsatellite markers at the five known loci. Prompted by the identification of a potentially shared haplotype near the RLS3 locus, we expanded the investigated linkage region on chromosome 9p using additional DNA markers.

Results: Mode of inheritance in our RLS family was compatible with an autosomal dominant pattern, and disease onset was mainly in childhood or adolescence. We excluded linkage to the RLS1, RLS2, RLS4, and RLS5 loci. However, we identified a likely new RLS gene locus (RLS3*) on chromosome 9p with a maximum lod score of 3.60 generated by model-based multipoint linkage analysis. A haplotype flanked by D9S974 and D9S1118 in a 9.9-Mb region, centromeric to RLS3, was shared by all 12 investigated patients. In addition, 11 of them carried a common haplotype extending telomeric to D9S2189 that is located within RLS3.

Conclusions: We demonstrate linkage to a locus on chromosome 9p that is probably distinct from RLS3. Our family with a rather homogeneous phenotype and very early disease onset represents a unique opportunity to further elucidate the genetic causes of the frequent restless leg syndrome.

Posted: Sat Mar 01, 2008 6:31 am
by ViewsAskew
Dr Poceta on Revolution Health talking about PLMD, RLS and the increased risk of heart disease: ... -hea-11801

Seems like there are a lot of other links to RLS info here, too. Might be a good read.

I quickly clicked on the RLS links and came up with this page: ... g-syndrome

All of his articles about RLS are there.

Posted: Tue Mar 04, 2008 5:02 am
by ViewsAskew
Yea! They are studying people in other countries, too! ... D=20080773

Two pedigrees with restless legs syndrome in Brazil.
Braz J Med Biol Res 2008;41(2):106-9.
Departamento de Psicobiologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil

Numerous studies have suggested a substantial genetic contribution in the etiology of the primary form of restless legs syndrome (RLS) and periodic leg movements (PLM). We describe the symptoms, the sleep profiles and physiological parameters of two families in which several members present RLS/PLM. The proband of family 1 is a 70-year-old woman and the proband of family 2 is a 57-year-old woman; both have exhibited the symptoms since the age of 20 years. All patients in both families were diagnosed with RLS according to the criteria of the International RLS Study Group. Polysomnographic recordings were performed to quantify and to describe PLM during sleep. Sleep parameters showed decreased sleep efficiency, increased sleep latency in the arousal index and the presence of PLM in all subjects. One of the families showed an exact profile of dominant inheritance with anticipation of age at onset. In the other family, the founders were blood relatives and there was no affected member in the third generation suggesting a recessive mode of inheritance. RLS/PLM is a prevalent sleep disorder affecting about 5 to 15% of the population and one that substantially impairs healthy sleep patterns. Efforts to understand the underlying pathophysiology will contribute to improve the sleep and life quality of these patients.

Posted: Thu Mar 27, 2008 4:09 am
by ViewsAskew
Age of onset and severity of RLS, with some references to PLMD, PLMW ... D=20081054

Age-at-onset in restless legs syndrome: a clinical and polysomnographic study.
Sleep Med 2007;9(1):54-9.
Sleep Disorders Center, Centre d'etude du sommeil et des rythmes biologiques, Hopital du Sacre-Coeur de Montreal, 5400 boul. Gouin Ouest, Montreal, Que., Canada H4J 1C5

OBJECTIVE: To determine the distribution of age-at-onset in a large cohort of patients with restless legs syndrome (RLS) and to compare clinical and polysomnographic characteristics of patients with early and late age-at-onset of RLS.

METHODS: Two hundred and fifty patients with RLS were studied. Information on age-at-onset, etiology, familial history and symptoms severity of RLS was obtained. Age-at-onset density functions were determined from bootstrap methods and kernel density estimators. RESULTS: Age-at-onset showed a significant bimodal distribution with a large peak occurring at 20 years of age and a smaller peak in the mid-40s. Early- and late-onset RLS could be separated with a cut-off at 36 years of age. Distributions of age-at-onset differed as a function of presence/absence of a familial history and etiology of RLS. Age-at-onset clearly differentiated patients with a primary RLS (early onset) from those with secondary RLS. Finally, early-onset RLS was associated with increased RLS severity with higher indices of periodic leg movements in sleep (PLMS) associated with microarousals and periodic leg movements during wakefulness (PLMW).

CONCLUSIONS: Early- and late-onset RLS could be distinguished depending on familial history and etiology of RLS. Our data suggest that different pathological processes are involved in these two groups, the early-onset group being highly genetically determined.

Posted: Sat Apr 26, 2008 6:52 pm
by ViewsAskew
Interesting new initiative and a study to go with it (and a web site). Short of it: many primary care/family doctors weren't confident in diagnosing RLS.

Now Available Online: Results of a Patient & Physician Survey on Leg Disorders

Professional Postgraduate Services® (PPS), renowned for its award-winning healthcare websites, is proud to announce the publication of Leg Disorders: Patient Behavior & Physician Effectiveness, the results of a collaborative Clinical Practice Survey with Harris Interactive, Inc. This publication reports the findings of two surveys designed in tandem to gauge physician competency in the diagnosis and management of leg disorders and, simultaneously, to investigate patient perspective and conduct in relation to leg disorders. Both surveys were also intended to assess the overall impact of leg disorders on patient quality of life.

Secaucus, NJ (PRWEB) April 24, 2008 -- Professional Postgraduate Services® (PPS), renowned for its award-winning healthcare websites, is proud to announce the publication of Leg Disorders: Patient Behavior & Physician Effectiveness Leg Disorders: Patient Behavior & Physician Effectiveness, the results of a collaborative Clinical Practice Survey with Harris Interactive, Inc. The survey and resulting publication were supported by an educational grant from AR Scientific, Inc. This publication was distributed via mail to target audience members, and is now also available on the official website of the Biology of Leg Disorders (BOLD®) educational initiative,

This publication reports the findings of two surveys designed in tandem to gauge physician competency in the diagnosis and management of leg disorders and, simultaneously, to investigate patient perspective and conduct in relation to leg disorders. Both surveys were also intended to assess the overall impact of leg disorders on patient quality of life.

Recruitment was from the American Medical Association's masterfile. The following qualifications were required for physicians to participate in the survey: currently practicing at the date of the survey, as well as for at least 2 years; spending at least half their time seeing patients; having no more than half their patients younger than age 18 years; and treating at least one patient with a leg disorder. A total of 815 participants were selected: 406 generalists comprising 102 family practitioners/general practitioners (FP/GP), 102 internal medicine physicians, 102 OB/GYNs, and 100 geriatricians; and 409 specialists comprising 103 cardiologists, 103 neurologists, 100 orthopedic surgeons, and 103 rheumatologists. Online interviews were conducted in August 2007. Questions were focused on nocturnal leg cramps (NLC), osteoarthritis, peripheral neuropathy, restless legs syndrome (RLS), gout, deep vein thrombosis (DVT), peripheral arterial disease (PAD), diabetic neuropathy, neuroleptic-induced akathisia, meralgia paresthetica (MP), and periodic limb movement disorder.

The survey found that of individuals with leg or feet symptoms (n=3,154), only 59% of the older population, aged 65+ years, and 36% of the younger population, aged 18-64 years, sought medical attention. Having decided to visit a physician, 75% went to an FP, and the mean number of visits prior to diagnosis ranged from 1.8 for gout to 3.3 for DVT. Patients were more likely than physicians to initiate a discussion about leg disorders, which sometimes were diagnosed as a result of a different primary complaint. In fact, 1 in 3 physicians responded that RLS is rarely or never diagnosed as a result of a patient's primary complaint. Physician confidence ranged by physician type and varied by disorder. Only 14% of OB/GYNs were highly confident in making a PAD diagnosis, while 100% of rheumatologists professed high confidence for diagnosing gout. Conditions for which a third or more FPs/GPs were not highly confident in diagnosis and treating included PAD, NLC, and RLS. Physician proficiency was measured by association questions and case studies for the various disorders. Correct responses for the cases ranged from 60% correct identification of MP to 95% correct identification of DVT. Treatment approaches, efficacy, and issues were investigated, with side effects of medication reported as a barrier to management by various percentages of patients in every leg disorder group. A high percentage of physicians thought leg disorders impaired quality of life; and patient responses revealed difficulties in daily functioning, especially sleep disruption. is the official website of the Biology of Leg Disorders (BOLD®) educational initiative. BOLD brings a first-of-its-kind educational paradigm to leg disorders, structuring programs across a spectrum of diseases. Classification that differentiates on the basis of pathophysiologic origin (ie, cardiovascular, neurologic, musculoskeletal) offers healthcare professionals comprehensive, cross-disciplinary education. currently features a dynamic slide library, current literature, CME-certified interactive case studies, clinical case videos and newsletters, "Ask the Expert" video podcasts, and the most recent addition, the Clinical Compendium on Leg Disorders, a consolidated body of knowledge on the broad spectrum of leg disorders and related comorbidities for primary care physicians, nurse practitioners, pharmacists, and other healthcare providers who treat patients with leg disorders. BOLD is truly a multimedia campaign with unprecedented outreach to clinicians. The Biology of Leg Disorders (BOLD®) educational initiative and are supported by an educational grant from AR Scientific, Inc.

Professional Postgraduate Services® (PPS)
Professional Postgraduate Services® (PPS) develops medical education activities designed to meet the needs of practicing physicians. PPS, working with medical leaders, designs and implements effective programs to meet specific educational objectives. Our overall goal is to conduct activities that will modify physician behavior in such a way as to have a positive impact on patient care and quality of life. Program formats are based on careful evaluation of message complexity, goals, audience needs, and budget, always taking advantage of proven training methodologies and interactivity. PPS develops medical education programs consistent with the Essentials and Standards of the Accreditation Council for Continuing Medical Education, as well as guidelines established by the AMA, PhRMA, and FDA. PPS is a business unit of KnowledgePoint360 Group, LLC, a leading healthcare information company.

Posted: Sat Apr 26, 2008 7:35 pm
by Aiken
The survey discussed in Ann's news release immediately above is here:

I'm reading it now. It's pretty interesting.

(My favorite part is where they also surveyed undiagnosed patients and have a graph of the "Effectiveness of doing nothing and waiting for the condition to go away" for several disorders. The RLS bar won't surprise anyone.)

Posted: Mon Apr 28, 2008 6:03 am
by ViewsAskew
Hmmm, a connection I don't think they've found before....wonder what this means in terms of treatment. Wish they'd offer this kind of speculation, lol. ... D=20081375

Group I nonreciprocal inhibition in primary restless legs syndrome.
Mov Disord 2008;23(1):96-100.
Department of Neurological Sciences, University of Bologna, Bologna, Italy.

Electrophysiological investigations of restless legs syndrome (RLS) have found spinal circuits impinging on motoneurones. We evaluated the H reflex threshold, latency, the Hmax/Mmax ratio, and the short latency autogenic inhibition in 7 patients with RLS and 10 age-matched controls by testing the excitability changes in soleus H reflex Ib interneuron function. A significant reduction in Ib inhibition at 4 (P = 0.043), 5 (P = 0.007), and 6 ms (P = 0.001) of H reflex conditioning interstimulus interval was found in RLS patients. Data support the hypothesis that altered group I nonreciprocal inhibition is implicated in enhancing the spinal circuitry excitability of RLS, and are consistent with the view of an abnormal supraspinal drive to spinal interneurons in RLS.

Posted: Tue Apr 29, 2008 7:12 pm
by ViewsAskew
As related to MS and cervical cord damage ... D=20081406

Mult Scler 2008;14(1):86-93.
Sleep Disorders Center, Scientific Institute and University Ospedale San Raffaele, Milan, Italy

In this prospective study, we estimated the prevalence of restless legs syndrome (RLS) in multiple sclerosis (MS) patients, and compared the extent of brain and cervical cord damage between patients with and without RLS using conventional and diffusion tensor magnetic resonance imaging (MRI). Eighty-two consecutive MS patients were evaluated. Each patient underwent a medical history interview, a neurological examination and brain/cervical cord MRI. Global and regional dual-echo lesion load (LL), number of cervical cord lesions, mean diffusivity (MD) and fractional anisotropy (FA) histograms metrics of the normal-appearing tissues of the brain and cervical cord were assessed. Thirty subjects had RLS; they showed a higher Expanded Disability Status Scale score than patients without. No difference between the two groups was found in whole brain, cerebellar and brainstem T(2)-LLs; MD and FA histograms derived metrics of the normal appearing brain tissues; basal ganglia MD; number of cervical cord lesions and cord MD histograms derived metrics. Cervical cord average FA was significantly reduced in MS patients with RLS compared to those without. RLS symptoms are very common in MS. This form of RLS should be considered as symptomatic. Higher disability and cervical cord damage represent a significant risk factor for RLS in MS patients.

RLE, Fibro, diabetes....and dopamine

Posted: Sat May 10, 2008 5:23 am
by ViewsAskew
This article is about the role of dopamine in many disorders that include pain: ... fm/ID/8842

Role of central dopamine in pain and analgesia - Source: Expert Review of Neurotherapeutics, May 2008

by Patrick B Wood


Recent insights have demonstrated a central role for dopaminergic neurotransmission in modulating pain perception and natural analgesia [pain reduction] within supraspinal [brain] regions, including the basal ganglia, insula, anterior cingulate cortex, thalamus and periaqueductal gray.

In addition, while the participation of serotonin and norepinephrine in spinal descending inhibition of pain is well known, a critical role for dopamine in descending inhibition [pain reduction at lower levels of the nervous system] has also been demonstrated.

Decreased levels of dopamine likely contribute to the painful symptoms that frequently occur in Parkinson's disease.

Moreover, abnormalities in dopaminergic neurotransmission have been objectively demonstrated in painful clinical conditions, including burning mouth syndrome, Fibromyalgia and restless legs syndrome.

Evidence from animal models and indirect evidence from pharmaceutical trials also suggest a role for dopamine in chronic regional pain syndrome and painful diabetic neuropathy.
Several novel classes of medication with analgesic properties have bearing on dopaminergic activity as evident in the capacity of dopamine antagonists to attenuate their analgesic capacity. [Dopamine 'antagonists' tend to 'turn down' dopamine activity.]

An expanded appreciation for the role of dopamine in natural analgesia provides the impetus for further study involving preclinical models and advanced neuroimaging techniques in humans, which may lead to the development of novel therapeutic strategies.

Source: Expert Review of Neurotherapeutics. 2008 May;8(5):781-97. PMID: 18457535, by Wood PB, Angler Biomedical Technologies, LLC, Jonestown, Texas, USA. [E-mail:]