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Posted: Sun Nov 09, 2008 1:06 am
by ViewsAskew
Well,they provedthat RLS got worse with relaxation...

Copied from NAPS

Cerebral correlates of muscle tone fluctuations in restless legs syndrome: a pilot study with combined functional magnetic resonance imaging and anterior tibial muscle electromyography.

Sleep Med 2008;9(2):177-83.
Department of Psychiatry and Psychotherapy, University Hospital, Hauptstrasse 5, 79104 Freiburg, Germany


BACKGROUND: The pathology of restless legs syndrome (RLS) is still not understood. To investigate the pathomechanism of the disorder further we recorded a surface electromyogram (EMG) of the anterior tibial muscle during functional magnetic resonance imaging (fMRI) in patients with idiopathic RLS. METHODS: Seven subjects with moderate to severe RLS were investigated in the present pilot study. Patients were lying supine in the scanner for over 50 min and were instructed not to move voluntarily. Sensory leg discomfort (SLD) was evaluated on a 10-point Likert scale. For brain image analysis, an algorithm for the calculation of tonic EMG values was developed. RESULTS: We found a negative correlation of tonic EMG and SLD (p <0.01). This finding provides evidence for the clinical experience that RLS-related subjective leg discomfort increases during muscle relaxation at rest. In the fMRI analysis, the tonic EMG was associated with activation in motor and somatosensory pathways and also in some regions that are not primarily related to motor or somatosensory functions. CONCLUSIONS: By using a newly developed algorithm for the investigation of muscle tone-related changes in cerebral activity, we identified structures that are potentially involved in RLS pathology. Our method, with some modification, may also be suitable for the investigation of phasic muscle activity that occurs during periodic leg movements.

Posted: Sun Nov 09, 2008 1:32 am
by ViewsAskew
I think we could have predicted this...

Restless legs syndrome is associated with DSM-IV major depressive disorder and panic disorder in the community.

J Neuropsychiatry Clin Neurosci 2008;20(1):101-5.
Division of Geriatric Psychiatry and Neuropsychiartry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.


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. Adjusted odds ratio for diagnosis of major depressive disorder (4.7, 95% confidence interval [1.6, 14.5]) and panic disorder (12.9 [3.6, 46.0]) and comorbidity of major depressive disorder and panic disorder (9.7 [1.4, 69.0]) in the past 12 months suggested a strong association between restless legs syndrome and major depressive disorder and/or panic disorder.

Posted: Tue Nov 11, 2008 2:58 pm
by cornelia
So true . Thanks Ann again, appreciate you posting these abstracts.

Posted: Tue Nov 11, 2008 6:53 pm
by ViewsAskew
Thank you, Corrie. I appreciate it.

Posted: Tue Nov 11, 2008 7:26 pm
by Polar Bear
Thanks Ann, you do so much work and research for us.


Posted: Tue Nov 11, 2008 8:59 pm
by ViewsAskew
Happy to do it as long as someone benefits, so it's good to know that people do.

Posted: Wed Nov 19, 2008 7:48 pm
by cornelia
Just read this on allergies and RLS:

Why Allergy Meds Worsen Restless Leg Syndrome - Histaminergic Clinical And Autopsy Abnormalities In Restless Legs Syndrome
18 Nov 2008

Johns Hopkins Researchers at Neuroscience 2008 - People with restless leg syndrome often have found that sleep-inducing allergy drugs worsen their symptoms. Now, researchers at the Johns Hopkins University School of Medicine have discovered a possible reason for that and help explain why RLS in general interferes with sleep but doesn't seem to result in daytime drowsiness. The common thread, the researchers say, is that histamine receptors - proteins found on the surface of some cells that are triggered by histamine - in the brain work to modulate nerve responses. When activated, histamine receptors stimulate alertness or wakefulness.

To sort out the relationship they suspected, the researchers first gave 12 RLS patients either a true sedative or diphenhydramine, the active ingredient in many allergy medications that tames histamine and induces sleepiness. They found that while sedatives had little to no effect on RLS, diphenhydramine made the RLS as much as three to four times worse. The team then looked at autopsied brains from RLS patients for possible differences in histamine receptor location and found that the substantia nigra, the part of the brain implicated in RLS, contained a higher number of histamine-3 receptor proteins, suggesting that this molecular pathway is more active in people with RLS.

"Five out of six patients in our study showed this elevated number of histamine receptor proteins," says Richard Allen, Ph.D., a research associate in neurology at Hopkins. "The histamine system appears to alter the balance of the nervous system so that one is not sleepy in the daytime, even with sleep loss, which might explain why RLS patients can get by on so little sleep. This also suggests that histamine receptors might be a new target for study and therapy of RLS."


Posted: Thu Nov 20, 2008 6:59 am
by ViewsAskew
I just love it when they prove what we've been saying for years...Yippee!

Posted: Thu Nov 20, 2008 5:27 pm
by jbj
Wow! I have been thinking about this for so long, and except for the discussion board, few people picked up on it. AFter reading the article, I understand why I can manage much better without sleep when caused by rls than other situations, but I can't say I understand why the antihistamines trigger more intense rls symptoms. Am I being dense?

Posted: Thu Nov 20, 2008 6:04 pm
by ViewsAskew
None of these abstracts make sense to a non-medical person unless you've read them thousands of times and start to "get" the jargon and implications. Even then, sometimes I am clueless. Often, however, since it's an abstract, they don't actually say why.

I am not sure, but I think this may be one of the areas that they just don't know yet. They clearly know that taking antihistamines makes RLS worse. And, they know we have more of these histamine receptors. But, as I read it, the inferences stop there.

I, however, am not a doctor! Or pharmacist, or nurse, or anything remotely connected to the medical field. If someone else gets more out of it...please pass it on.

Posted: Fri Nov 21, 2008 10:51 pm
by Neco
I have found interesting information! HAH! ... d_RVDocSum

Locomotion is increased in a11-lesioned mice with iron deprivation: a possible animal model for restless legs syndrome.

Qu S, Le W, Zhang X, Xie W, Zhang A, Ondo WG.

Departments of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA.

Restless legs syndrome (RLS) is a common neurologic condition involving iron and dopamine systems. We sought to create an animal model consistent with RLS based on current understanding of human pathology. We performed bilateral 6-hydroxydopamine (6-OHDA) lesioning in the A11 nucleus of C57BL/6 mice and deprived a subset of mice from dietary iron to observe whether these manipulations can increase motor activity. Iron levels in serum, brain, and especially spinal cord were significantly decreased after iron deprivation. Interestingly, 6-OHDA lesioning appeared to further reduce CNS iron stores. Pathologic examination demonstrated a 94% reduction in A11 tyrosine hydroxylase staining cells in mice injected with 6-OHDA but minimal effects on other areas. Locomotor activities were significantly increased in both the mice that were iron deprived and the A11-lesioned mice compared with controls. The combination of iron deprivation and A11 lesions further significantly augmented activity. Additionally, the mice in the combined iron-deprived and lesioned group were more aggressive. The increased activity in A11-lesioned mice with or without iron deprivation was normalized after treatment with the D2/D3 agonist ropinirole, as is seen in human RLS but was worsened by the D1 agonist SKF38393. This model could be consistent with human RLS, attention deficit hyperactivity disorder, or akathisia.

Posted: Fri Nov 21, 2008 10:57 pm
by Neco
Here are some related postings from the same person. ... d_RVDocSum
Animal models of restless legs syndrome.

Ondo WG, Zhao HR, Le WD.

Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.

Restless legs syndrome (RLS) is a common disease with prevalence up to 10% in the general population. It is mostly a subjective condition, making animal models intrinsically difficult. General increased activity (urge to move) and limb movements consistent with periodic limb movements of sleep, seen in most patients with RLS, are currently our best behavioral markers. Our best understanding of human RLS demonstrates reduced central nervous system (CNS) iron stores and dysfunction of dopaminergic systems, which most likely involves the spinal cord. Based upon this knowledge, animal manipulations, including destruction of the A11 diencephalic-spinal tract and iron deprivation, have resulted in animal behavior consistent with RLS. Dopamine receptor type 3 knockout mice also show general increased activity. Pharmacologic blockade of dopamine receptors in rodents has also caused movements resembling periodic limb movements of sleep in older rodents but not in younger animals. More sophisticated animal modeling is needed to facilitate our understanding of RLS. ... d_RVDocSum

Spinal cord dopamine receptor expression and function in mice with 6-OHDA lesion of the A11 nucleus and dietary iron deprivation.

Zhao H, Zhu W, Pan T, Xie W, Zhang A, Ondo WG, Le W.

Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA.

It is suggested that dysfunction of the diencephalospinal dopaminergic (DAergic) pathway may cause restless legs syndrome. We examined the mRNA and protein levels as well as DA receptor subtypes function within the lumbar spinal cord of an RLS animal model. C57BL/6 male mice with or without iron deprivation were lesioned with 6-hydroxydopamine (6-OHDA) in the bilateral A11 nuclei. Locomotor behaviors were observed. DA concentration, mRNA, and protein levels of D1, D2, and D3 receptors in the lumbar spinal cords were analyzed, and the specific binding of D1, D2, and D3 receptors was determined using [(3)H]SCH23390, [(3)H]Spiperone, and [(3)H]PD128907 radioligands respectively. The behavioral tests showed that the locomotor activities were increased significantly in the mice treated with iron-deficiency (ID) diet and 6-OHDA lesions, which were reversed by the D2/D3 agonist ropinirole. DA in the spinal cord was decreased significantly by 6-OHDA lesioning in A11. D2/D3 mRNA and protein levels as well as their binding capacity in the spinal cord were decreased significantly by 6-OHDA lesions. ID with 6-OHDA lesions produced a synergistic greater decrease of D2 binding. Although ID increased D1 mRNA and protein expression in the spinal cord, it did not significantly change D1 receptor binding. The present study suggests that ID and 6-OHDA lesions in A11 nuclei differentially altered the D1, D2, and D3 receptors expression and binding capacity in the lumbar spinal cord of RLS animal model, which was accompanied by changes in locomotor activities. (c) 2007 Wiley-Liss, Inc.

Sorry if any of this was posted before, this thread is huge!

Posted: Sat Nov 22, 2008 8:13 am
by ViewsAskew
Yeah, it is huge by now. You know, I heard about those mice....but I'm not sure it was posted. It could have been Dr Ondo talking about it at a conference...

Thanks, Zach. I am thrilled when other people post in here, too.

Posted: Thu Dec 25, 2008 11:11 pm
by ViewsAskew
I didn't like reading the following at all... :(

Sleep Med Rev. 2008 Dec 16.
Melatonin, sleep disturbance and cancer risk.

Blask DE.

The pineal hormone melatonin is involved in the circadian regulation and facilitation of sleep, the inhibition of cancer development and growth, and the enhancement of immune function. Individuals, such as night shift workers, who are exposed to light at night on a regular basis experience biological rhythm (i.e., circadian) disruption including circadian phase shifts, nocturnal melatonin suppression, and sleep disturbances. Additionally, these individuals are not only immune suppressed, but they are also at an increased risk of developing a number of different types of cancer. There is a reciprocal interaction and regulation between sleep and the immune system quite independent of melatonin. Sleep disturbances can lead to immune suppression and a shift to the predominance in cancer-stimulatory cytokines. Some studies suggest that a shortened duration of nocturnal sleep is associated with a higher risk of breast cancer development. The relative individual contributions of sleep disturbance, circadian disruption due to light at night exposure, and related impairments of melatonin production and immune function to the initiation and promotion of cancer in high-risk individuals such as night shift workers are unknown. The mutual reinforcement of interacting circadian rhythms of melatonin production, the sleep/wake cycle and immune function may indicate a new role for undisturbed, high quality sleep, and perhaps even more importantly, uninterrupted darkness, as a previously unappreciated endogenous mechanism of cancer prevention.

Posted: Sat Jan 10, 2009 10:21 pm
by ViewsAskew
I wish I had a subsrciption to NEJM, but alas I do not...if anyone does and wants to give the full text, that would be wonderful!

Wait! I found it! Right here at the Foundation. Thank you, Foundation!

Periodic Limb Movements in Sleep — Endophenotype for Restless Legs Syndrome?
John W. Winkelman, M.D., Ph.D.

Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

Today, 350 years after its first description, the restless legs syndrome (RLS) is strangely controversial. Experts and patients alike describe RLS both as a miserably impairing disorder and as "the most common disorder you have never heard of." Critics do not regard RLS as a disorder at all but, rather, as the fabrication of an omnivorous pharmaceutical industry. RLS is a waking sensorimotor disturbance with features of both neurologic and sleep disorders. Those afflicted describe an intensely uncomfortable, overwhelming urge to move the legs (often accompanied by dysesthesias), predominantly in the evening or at night, that is present at rest . . . [Full Text of this Article] (which you have to be a subscriber to get...)

Link to whole article