Page 4 of 33

Posted: Sat Nov 08, 2008 10:30 pm
by ViewsAskew
This oneis for those pregnant or wishing to be pregnant.

Copied from NAPS

Medications for restless legs syndrome in pregnancy.

J Obstet Gynaecol Can 2008;30(6):505-7.
The Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, University of Toronto, Toronto ON


According to epidemiological data, pregnant women have a two or three times higher risk of experiencing restless legs syndrome (RLS) than the general population. Current evidence suggests that dopaminergic dysfunction, impaired iron homeostasis, and genetic predisposition may be involved in the pathophysiology of RLS. Four classes of medications have been used for patients with RLS, but pregnancy elicits a therapeutic concern. Although two dopamine agonists, ropinirole and pramipexole, have been approved by the FDA for the treatment of RLS and are currently the first-line treatment for daily symptoms, there is very little information on the teratogenic risks of these new medications. Therefore, they are not currently recommended for use during pregnancy. Medications with a more extensive safety record in pregnancy include opioids; antiepileptics, such as carbamazepine and gabapentin; and certain benzodiazepines. Ruling out iron deficiency should be an integral part of a treatment plan for RLS in pregnancy. Before management with medication is introduced, every patient should be assessed for iron status with measurement of serum ferritin.

Posted: Sat Nov 08, 2008 10:36 pm
by ViewsAskew
Susan, you may appreciate this, as well as anyone with circadian delay problems.

Copied from NAPS

ramelteon administration in healthy adults.

J Clin Sleep Med 2008;4(5):456-61.
Henry Ford Hospital, Sleep Center, 2799 West Grand Blvd., CFP-3, Detroit, MI 48202, USA.


STUDY OBJECTIVES: To assess the ability of repeated daily oral ramelteon to facilitate re-entrainment of human circadian rhythms after an imposed phase advance of the sleep-wake cycle. METHODS: A total of 75 healthy adult volunteers aged 18-45 years remained in a sleep laboratory for 6 days and 5 nights; a 5-h phase advance in their sleep-wake cycle was imposed under dim-light conditions. Oral ramelteon (1,2, 4, or 8 mg once daily for 4 days) or placebo was administered 30 min before bedtime. The primary endpoint was the phase of the circadian rhythm as assessed by the time at which salivary melatonin concentrations declined below 3 pg/mL after morning awakening (dim-light melatonin offset [DLMoff]). RESULTS: After 4 days of once-daily treatment, participants receiving 1, 2, or 4 mg ramelteon exhibited statistically significant phase shifts in DLMoff of -88.0 (16.6), -80.5 (14.8), and -90.5 (15.2) minutes respectively, versus -7.1 (18.6) minutes for placebo (least-squares mean(SEM), p = 0.002, p = 0.003, p = 0.001, respectively). Change in DLMoff for the 8 mg dose of ramelteon, -27.9 (16.4) minutes, was not significantly different than that for placebo (p = 0.392). CONCLUSIONS: Ramelteon (1, 2, or 4 mg per day) administered before bedtime significantly advanced the phase of the circadian rhythm after a 5-h phase advance in the sleep-wake cycle. These findings suggest that ramelteon has potential as a specific therapy for circadian rhythm sleep disorders.

Posted: Sat Nov 08, 2008 10:48 pm
by ViewsAskew
More implicating iron's role in RLS.

Copied from NAPS

Pathophysiology of restless legs syndrome: evidence for iron involvement.

Curr Neurol Neurosci Rep 2008;8(2):162-6.
G.M. Leader Family Laboratory, Department of Neurosurgery, Pennsylvania State University, Milton S. Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033, USA.


Neuroimaging, analysis of cerebrospinal fluid, and studies on postmortem tissue are generating data that support the concept that iron availability to the brain is a contributory process to, if not a cause of, restless legs syndrome. These data are reviewed and related to the dopaminergic system because of the use of dopamine agents in treating restless legs syndrome.

Posted: Sat Nov 08, 2008 10:57 pm
by ViewsAskew
About PLMsin general.

Copied from NAPS

Periodic limb movements during sleep: population prevalence, clinical correlates, and racial differences.

Sleep 2008;31(9):1221-7.
Sleep Disorders and Research Center Henry Ford Hospital, Detroit, MI 48202, USA


STUDY OBJECTIVE: There is growing interest in the study of periodic limb movements during sleep and their potential clinical correlates. The aim of the present analysis is to address the lack of population-based studies using polysomnographic (PSG) measures to determine the prevalence of period limb movements during sleep in specific racial groups as well as the general population. SETTINGS AND PARTICIPANTS: A community-based sample of 592 participants drawn from the general population of tricounty Detroit (mean age = 41.9 +/- 12.6 years; 52.9% F; 31.5% African American). All individuals were assessed using objective and subjective measures in the sleep laboratory. MEASUREMENTS: Participants were evaluated during a 24-h laboratory assessment, including a polysomnogram and multiple sleep latency test. Periodic leg movements were scored using standard criteria. Reports of sleep disturbance and daytime sleepiness were also assessed using standardized measures including the Global Sleep Assessment Questionnaire (GSAQ) and the Epworth Sleepiness Scale (ESS). RESULTS: The overall prevalence of periodic limb movements during sleep (PLMSI >15) was 7.6%. African Americans had a lower prevalence of PLMSI >15 than Caucasians (4.3% vs. 9.3%; chi2= 4.5, P < 0.05). Regardless of race, symptoms of insomnia were significantly higher in individuals with PLMSI >15 than in those with PLMSI < or =15 (45% vs. 25%; chi2= 6.84, P < 0.01). CONCLUSION: This is the first study to determine the prevalence of PLMS in a population-based sample using standardized objective criteria. A key finding of the present study is that racial differences in this PSG parameter do exist, with African Americans being less likely to have elevated PLMS.

Posted: Sat Nov 08, 2008 11:00 pm
by ViewsAskew
And, yet another linking ironin the brain to RLS.

Copied from NAPS

T2 relaxometry and fMRI of the brain in late-onset restless legs syndrome.

Neurology 2008;71(12):911-6.
Department of Radiology, Medical School University of Ioannina, Greece


OBJECTIVE: To assess in patients with late-onset idiopathic restless legs syndrome (RLS) the brain iron content with magnetic resonance relaxometry, and brain activation during dorsiflexion and plantar flexion of both feet, using fMRI. METHODS: The study was approved by the institutional review board, and informed consent was obtained. Twenty-five RLS patients (14 women, 11 men; age range 55-82 years; mean 66.5 +/- 8.9 years; disease duration 6.5 +/- 4.5 years) and 12 sex- and age-matched controls were studied. A T1-weighted high-resolution three-dimensional spoiled gradient echo sequence was used for structural imaging, a multislice spin echo Tau2-weighted sequence was used for T2 relaxometry, and a single-shot multislice gradient echo planar sequence was used for fMRI. The motor paradigm consisted of alternating periods of rest and movement, each 40 seconds in duration. Region of interest analysis was used on the T2 relaxometry maps. Statistical parametric mapping software was used for analysis of the functional data. RESULTS: T2 relaxation time was significantly higher in patients than in controls in the substantia nigra pars compacta. Within-group analysis showed that both patients and controls activated the primary motor cortex, the primary somatosensory cortex, the somatosensory association cortex, and the middle cerebellar peduncles. Patients also activated the thalamus, putamen, middle frontal gyrus, and cingulate gyrus. Between-group analysis showed that patients had higher activation of the dorsolateral prefrontal cortex. CONCLUSION: Late-onset restless legs syndrome is associated with low iron content of the basal ganglia and increased activity of the dorsolateral prefrontal cortex.

Posted: Sat Nov 08, 2008 11:02 pm
by ViewsAskew
There is no abstract for this, too bad.

[Electromagnetic therapy in restless legs syndrome and nocturnal leg muscle cramps. Same effect of pulsating electromagnetic fields and placebo]
Lakartidningen 2008;105(32-33):2167-70.
[ no abstract ]

If anyone has access to this (or time to search for it), please post.

Posted: Sat Nov 08, 2008 11:08 pm
by ViewsAskew
This study is about PLMS and pramipexol's rolein treating leg movements.

Copied from NAPS

Defining the boundaries of the response of sleep leg movements to a single dose of dopamine agonist.

Sleep 2008;31(9):1229-37.
Sleep Disorders Center, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Vita-Salute University, Milan, Italy.


STUDY OBJECTIVES: To define which leg movements (LM) associated with restless legs syndrome (RLS) respond to dopamine-agonist treatment and verify if they fall within current diagnostic criteria for periodic LM during sleep (PLMS). DESIGN: Single-blind placebo-controlled study. SETTINGS: Sleep laboratory. PATIENTS: 43 consecutive untreated patients with idiopathic restless legs syndrome. INTERVENTIONS: Patients underwent clinical and neurophysiological evaluation, hematological screening, and 2 consecutive full-night polysomnographic studies. Before the second polysomnographic study, all patients were randomized to receive 0.25 mg of pramipexole or placebo. MEASUREMENTS AND RESULTS: LM parameters such as duration, amplitude, interval, and periodicity were analyzed. Compared to placebo, pramipexole significantly (P < 0.01) reduced PLMS while increasing sleep efficiency. Specifically we observed a significant (P < 0.01) reduction in LM ranging 2-4 s in duration and with intermovement interval of 6-46 s and a significant decrease in the periodicity of motor events. No effect of pramipexole was observed on isolated LM. CONCLUSIONS: These results support a heterogeneous basis for LM in RLS patients; while isolated LM do not respond to pramipexole treatment, most, but not all, PLMS classified by means of the current criteria do. Further studies with different pramipexole doses or dopamine agonists with different receptor-binding preference are warranted to better define the borders of dopamine response of PLMS.

Posted: Sat Nov 08, 2008 11:23 pm
by ViewsAskew
Sometimes I wish they'd write in English instead of doctorese...

This appears to be about a new gene locus identified as related to RLS.

PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome.

Nat Genet 2008;40(8):946-8.
Institute of Human Genetics, Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Neuherberg 85764, Germany


We identified association of restless legs syndrome (RLS) with PTPRD at 9p23-24 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czechia and Canada. Two independent SNPs in the 5' UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4626664, P(nominal/lambda corrected) = 5.91 x 10(-10), odds ratio (OR) = 1.44; rs1975197, P(nominal/lambda corrected) = 5.81 x 10(-9), OR = 1.31). This work identifies PTPRD as the fourth genome-wide significant locus for RLS.

Posted: Sun Nov 09, 2008 12:07 am
by ViewsAskew
This is interesting because it appeals to the theory that RLS is not a disorder with only one cause. It will be interesting to see how they untangle all of this in the end. Thishas to do with possibility of venous disease and treating RLS.

The effect of endovenous laser ablation on restless legs syndrome.

Phlebology 2008;23(3):112-7.
Vein Center of North Texas, Denison, Texas, USA.


OBJECTIVES: Venous disease was proposed as a cause of restless legs syndrome (RLS) by Dr Karl A Ekbom in 1944, but has since remained largely unexplored. This study examines the effect of endovenous laser ablation (ELA) in patients with concurrent RLS and duplex-proven superficial venous insufficiency (SVI). METHODS: Thirty-five patients with moderate to very severe RLS (as defined by the 2003 National Institute of Health (NIH) RLS criteria) and duplex-proven SVI completed an international RLS rating scale questionnaire (IRLS) and underwent standard duplex examination to objectively measure the baseline severity of their conditions. They were separated into non-operative and operative cohorts. The operative cohort underwent ELA of refluxing superficial axial veins using the CoolTouch CTEV 1320 nm laser and ultrasound-guided sclerotherapy of the associated varicose veins with foamed sodium tetradecyl sulphate (STS). All patients then completed a follow-up IRLS questionnaire. Baseline and follow-up IRLS scores were compared. RESULTS: Operative correction of the SVI decreased the mean IRLS score by 21.4 points from 26.9 to 5.5, corresponding to an average of 80% improvement in symptoms. A total of 89% of patients enjoyed a decrease in their score of > or =15 points. Fifty-three percent of patients had a follow-up score of < or =5, indicating their symptoms had been largely alleviated and 31% had a follow-up score of zero, indicating a complete relief of RLS symptoms. CONCLUSIONS: ELA of refluxing axial veins with the CTEV 1320 nm laser and foamed STS sclerotherapy of associated varicosities alleviates RLS symptoms in patients with SVI and moderate to very severe RLS. RECOMMENDATIONS: SVI should be ruled-out in all patients with RLS before initiation or continuation of drug therapy.

Posted: Sun Nov 09, 2008 12:12 am
by ViewsAskew
This study strives to create a relationship between several diseases and RLS.

Attention-deficit/hyperactivity disorder, Tourette's syndrome, and restless legs syndrome: the iron hypothesis.

Med Hypotheses 2008;70(6):1128-32.
APHP, Child and Adolescent Psychopathology Unit, Robert Debre Hospital, Paris VII University, Paris, France.


Preliminary but increasing evidence suggests that attention-deficit/hyperactivity disorder (ADHD), Tourette's syndrome (TS), and restless legs syndrome (RLS) may be comorbid. In the present article, we hypothesize that ADHD, TS, and RLS may be part of a spectrum, and that iron deficiency contributes to the pathophysiology underlying this spectrum. Iron deficiency might lead to ADHD, RLS and TS symptoms via its impact on the metabolism of dopamine and other catecholamines, which have been involved into the pathophysiology of ADHD, TS, and RLS. We speculate that the catecholaminergic systems are differently impacted in each of the three disorders, contributing to a different specific phenotypic expression of iron deficiency. MRI studies assessing brain iron levels in ADHD, TS, and childhood RLS, as well as genetic studies on the specific molecular pathways involved in iron deficiency, are greatly needed to confirm the iron hypothesis underlying ADHD, TS, and RLS. This body of research may set the basis for controlled trials assessing the effectiveness and tolerability, as well as the most appropriate dose, duration and type (oral vs. intravenous) of iron supplementation. In conclusion, the iron hypothesis may help us progress in the understanding of pathophysiological links between ADHD, RLS, and TS, suggesting that iron supplementation might be effective for all these three impairing conditions.

Posted: Sun Nov 09, 2008 12:24 am
by Aiken
Wow, that's an interesting one. I actually know someone who has ADHD, occasional RLS, and a touch of Tourette's. Should be interesting to see if they can get anywhere with it.

Posted: Sun Nov 09, 2008 12:25 am
by ViewsAskew
Too bad we can't see the whole article...I'd really like to see his conclusions; this is just a synopsis.

Copied from NAPS

Effectiveness of benzodiazepines: do they work or not?

Expert Rev Neurother 2008;8(8):1189-91.
P056, Institute of Psychiatry, King's College, London, Denmark Hill, London, SE5 8AF, UK.


The benzodiazepines have been extensively prescribed for decades for vague indications such as anxiety, sleeplessness and muscle tension. Despite increasing knowledge of their adverse effects, such as sedation, psychomotor and cognitive impairment, and dependence on long-term use, and the recent advent of better alternatives, their use continues largely unabated. The paper under review assesses the sparse high-quality data related to efficacy (denoted by the dropout rate for failure to respond), effectiveness (dropout rate for any reason) and dropout for adverse effects. The conclusion is that efficacy was significantly higher for the drugs as compared with placebo; by contrast, no convincing evidence was found of any short-term effectiveness: and adverse effects were 1.5-times more frequent in the drug-treated patients. Various reasons for these results are discussed. I point out the changes in diagnostic criteria over the years and the lack of accepted methods of assessing estimates of effectiveness in clinical practice. Excessive prescribing of these controversial drugs is likely to continue.

Posted: Sun Nov 09, 2008 12:53 am
by ViewsAskew
Huh...OK, so it works regardless of your serum ferritin, but is there a relationship to augmentation?

Copied from NAPS

Response to ropinirole in restless legs syndrome is independent of baseline serum ferritin.
J Neurol Neurosurg Psychiatry 2008;79(8):964-5.
[ no abstract ]

Posted: Sun Nov 09, 2008 1:01 am
by ViewsAskew
More about iron and ADHD...seems something that is worth looking into, huh?

For Some Kids, ADHD Behavior Is a Sign of Low Iron

Member since:
March 26, 2007
For Some Kids, ADHD Behavior Is a Sign of Low
July 29, 2008 04:19 PM EDT (Updated: July 30, 2008 10:36 AM EDT)
views: 1587 | rating: 10/10 (2 votes) | comments: 3

My six-year-old son Casey has always been a busy child, and he barely touches down at the table to eat his meals. I take pride in being a parent who is non-alarmist, and I’ve never really been concerned about his choosy eating until this year. I put three nutritious meals in front of him each day, and I figured he would eat if he needed to eat.

My pediatrician once told me, “Kids don’t always eat well every day, but if you average out what they eat in the course of a week, they usually get what they need.”

My husband also pointed out, “He poops enough, so he must be eating enough.” This seemed so rational, I found it reassuring.

Casey certainly has always taken in adequate calories. He is a bundle of energy, usually climbing across our furniture or racing around our home. What calories he misses at mealtime, he has always made up for by drinking milk. He loves milk, and always has. It takes my constant attention to make sure that we don’t run out of milk in our house—left to his own devices, Casey could go through a half gallon in a day.

But this year Casey has had trouble. In the second half of his kindergarten year, his learning curve flattened and he stopped showing interest in learning how to read. He stopped listening well at school, sometimes gazing off in a trance, or fidgeting badly during quiet times, incapable of paying attention. At other times he was dramatically hyperactive, disrupting the class or racing up and down trees and around his school. He was impulsive at home—hitting his baby brother over the head after only minor provocations.

Our Casey had all the signs of attention deficit hyperactivity disorder (ADHD), a problem that typically begins at his age or shortly afterwards. ADHD affects boys far more often than girls. The three behavior patterns that occur in ADHD are inattention, impulsive behavior, and hyperactivity. At the request of our pediatrician, I asked his teachers to fill out a questionnaire about Casey. The questionnaire was the Connors’ Rating Scale, a series of questions that is used to give a child a score that describes his behavior. If the score is very high, it is likely the child has ADHD.

We brought Casey to a psychologist to learn the results of the test. “I have never seen a rating scale like Casey’s from his teachers,” he said. “He scored at the most extreme level for almost every question.”

I reflected about his abrupt change this year. He seemed to be regressing in many ways—he began sleeping in our bed again, he began to chew on Kleenex tissues instead of blowing his nose with them, and he chewed on small parts from his toys, like the tires from his Lego cars. He also began to chew the sleeves and the collars of his shirts, soaking his front with saliva and shredding his shirts as he chewed. This chewing was not a typical part of ADHD. In fact, it was bizarre.

As I thought about Casey and his incessant chewing, I had an important idea.

The body’s quest for iron

As a primary care doctor, I take care of adults. When my patients have low iron levels, they have telltale signs. They lack energy, they get tired more easily with exercise, they sometimes complain of headaches, and they may be pale. In addition to these symptoms, iron deficiency causes curious cravings—an urgent need to chew ice, for example. Ice doesn’t contain iron, so ice crunching doesn’t help the problem. Yet as strange as it may seem, ice crunching is a fairly useful clue to doctors that the iron might be low.

Children don’t always pay attention to what is and is not edible when they put things into their mouths. Some children develop cravings to chew on many things when they need more iron— paper, paint chips, clay, dirt, you name it. This eating of non-nutritive items is called “pica.” Pica is not always caused by iron deficiency, but low iron frequently is the cause.

Could Casey’s shirt-chewing and toy-chewing come from iron deficiency? As soon as I asked myself this question, I knew it was likely.

Most adults with low iron get that way by losing blood—for example, from intestinal bleeding or, for women, from heavy periods. Most adult Americans get plenty of iron in their diets. But anyone who binges on a favorite food can eat a less varied diet than is needed. This is true for an alcoholic, who gets calories from beer or liquor and who has inadequate hunger for nutritious food. This is also true for children with a favorite food, particularly children who drink too much milk. Thirteen percent of young grade school children are iron deficient. Casey was one of these kids.

Beyond anemia: Iron’s subtle effects in the brain

Most people understand that low iron leads to anemia and feelings of fatigue. Most people don’t know about the more curious troubles that low iron can provoke.

For instance, restless legs syndrome—an urge to move the legs when you are in bed at night—can be caused by low iron. Restlessness of the legs may be caused by a change in the brain hormone “dopamine.” A change in dopamine can be related to your iron level. Iron has to be available in adequate amounts for your brain to keep its dopamine at a normal level.

ADHD is not perfectly understood, but it occurs when there is a change in brain chemistry. Medicines like Ritalin that alter brain chemistry can improve ADHD symptoms. One of the hormone shifts that can trigger ADHD is, in fact, a change in the dopamine level.

Can low iron cause symptoms that mimic ADHD? Yes, in some cases it can. On average, children with ADHD have lower iron levels than is normal. Some children with ADHD behaviors have strikingly low iron levels. When these children get their iron levels to normal by taking iron supplements, they can have a slow but steady improvement in their attention and hyperactivity.

Casey’s iron deficiency was obvious once we had his blood tested. His blood count (hematocrit) was seven points lower than what is average for his age, and his iron test was very low. We have changed our dinner menu to bring on the red meat, and he is taking iron supplements twice a day. Slowly, slowly, but surely, Casey is regaining his listening and his self-control.

The connection between iron and ADHD has only been recognized by doctors during the last five to ten years. Only a few small studies have been published to explore the connection. Feeling hopeful, some doctors have tried treating children who had ADHD with iron supplements even when the children had normal iron levels. But this didn’t work--children who start out with normal iron levels don’t appear to have any change in their behavior when iron is replaced. Reviewing these results, experts agree that children who don’t need extra iron should not be given supplements. When it is overdone, iron supplementation can actually be dangerous.

So far, testing iron has not become a standard part of the medical evaluation for children with ADHD behavior. For a few children with ADHD, iron is the issue. If your child has behavior like ADHD, I recommend asking your doctor to arrange a blood test that can check for iron deficiency. Even in a home where food is abundant, it is easy enough for a child to get too little iron.

Do you know a child with ADHD? If so, do you know whether iron has been tested? Do you have good advice for parents whose children are picky eaters?

Mary Pickett, M.D., is an Associate Professor of Medicine at Oregon Health & Science University where she is a primary care doctor for adults. Her field is Internal Medicine. She is also a Lecturer for Harvard Medical School and a Senior Medical Editor for Harvard Health Publications.

Posted: Sun Nov 09, 2008 1:03 am
by ViewsAskew
To conclude that there is no role for anticonvulsants in RLS...double huh.

Anticonvulsants to treat idiopathic restless legs syndrome: systematic review.

Arq Neuropsiquiatr 2008;66(2b):431-435.
Department of Emergency Medicine and Evidence Based Medicine, Universidade Federal de Sao Paulo, SP, Brazil


BACKGROUND: Restless legs syndrome (RLS) is a sensory motor disorder characterized by a distressing urge to move the legs and sometimes also other parts of the body usually accompanied by a marked sense of discomfort or pain in the leg or other affected body part. Many treatments have been used to minimize the discomfort of the disease, among them the anticonvulsant therapy. AIM: This review aims to evaluate the efficacy and safety of anticonvulsant treatment for idiopathic RLS. METHOD: Systematic review of randomized or quasi-randomized, double blind trials on anticonvulsant treatment for RLS. Outcomes: relief of RLS symptoms, subjective and objective sleep quality, quality of life, and adverse events associated with the treatments. RESULTS: A total of 231 patients were randomized in three cross over studies and one parallel study. Three studies with carbamazepine, one with sodium valproate, and one with gabapentin, and they were very heterogeneous so we could not perform a metanalyses. CONCLUSIONS: There is no scientific evidence on RLS treatment with anticonvulsants for clinical practice.